1110 results about "Signal Pathways" patented technology

The invention belongs to the technical field of medicines, and particularly relates to quinazoline stilbene derivatives as well as a preparation method, a composition and application thereof. The quinazoline stilbene derivative is synthesized by combining quinazoline with pharmacophores such as a styrene skeleton, and the quinazoline stilbene derivative structurally contains functional units such as a quinazoline functional unit and the pharmacophores such as the styrene skeleton, so that the compound is endowed with good anti-tumor activity. Researches show that the quinazoline stilbene derivative has a good anti-tumor effect including KRASG12C mutation non-small cell lung cancer, has the advantage of multi-target action, has an adjusting effect on Src kinase and related downstream signal channels of Statat, mTOR, Akt and PI3k, and is beneficial to reduction of tumor drug resistance. Compared with a complex structure modified compound, the quinazoline stilbene derivative disclosed by the invention is simple in structure and easy to prepare, and has a good application prospect.

Disclosed in the present invention is a new substituted heterocyclic compound having GSPT1 degradation activity, and particularly disclosed is a compound having the structure as shown in formula (I) as a GSPT1 degradation agent, or a pharmaceutically acceptable salt, a solvate, a hydrate, an isotope substitute or an isomer thereof. The compound can be used for preventing or treating diseases related to GSPTs / MYC targets or signaling pathways.

The invention relates to a heart organoid and an in-vitro preparation method thereof, and belongs to the technical field of stem cells. The invention provides a heart organoid. The heart organoid is obtained by induced culture of an adherent pluripotent stem cell mass; the adherent pluripotent stem cell mass is obtained by adherent culture of a suspended pluripotent stem cell mass; the suspension pluripotent stem cell mass is obtained by suspension culture of pluripotent stem cells. According to the in-vitro preparation process of the heart organoid, after pluripotent stem cells form balls, the pluripotent stem cell balls are subjected to staged induced differentiation under adherent culture, so that cell subtypes such as epicardial cells and the like can be generated without additional addition or additional stimulation of signal channels, and the heart organoid is more homogeneous. The self-occurring multi-lineage coexisting heart organoid can better simulate biological events derived from multiple cell types and multiple cell subtypes in the early development process of an embryonic heart, and has great application prospects in exploration of pathogenic factors and potential treatment targets of congenital heart diseases.

The invention belongs to the field of daily chemicals, and provides a composition with a longevity gene activation effect, a product containing the composition and application of the composition, and the composition provided by the invention comprises hexapeptide, chlamydomonas and cornflower extract. The hexapeptide, the chlamydomonas nivalis and the cornflower extract are compounded for use, so that the expression of longevity genes KLOTHO and SIRT1 can be remarkably improved. Once the longevity gene serving as the upstream of a signal regulation pathway is activated, various downstream signal pathways can be regulated, such as inhibition of expression of inflammation-related genes, promotion of DNA repair, telomere homeostasis, gene expression of mitochondrial energy and the like, promotion of synthesis of collagen and the like, and finally, longevity of cells and improvement of skin phenotypes are promoted. The effects of resisting wrinkles, tightening and the like are achieved. Therefore, the composition provided by the invention can activate long-life gene expression and regulate and control multiple signal pathways, has potential effects of improving light aging, tightening and resisting wrinkles and the like, and is an anti-aging composition with great potential.

The invention belongs to the technical field of biological medicine, and particularly relates to a manganese-doped zeolite imidazole framework and application thereof in tumor radiotherapy. According to the present invention, the new use of the manganese-doped zeolite imidazole framework as the tumor radiosensitizer is found, Mn-ZIF-8 has ray responsiveness, can continuously release Mn < 2 + > ions under X-ray irradiation, and can enhance the activation of a cGAS-STING signal channel so as to promote DCs maturation and antigen presentation, and enhance the T cell mediated immune response, such that the tumor treatment effect is enhanced. Furthermore, the invention provides the Mn-ZIF-8 microneedle, the microneedle has the characteristics of rapid dissolution and controlled release, ensures accurate delivery and continuous action of drugs at tumor sites, reduces systemic toxicity, and can significantly amplify local and systemic immune effects caused by radiotherapy and improve the therapeutic effect when used in combination with an immune checkpoint inhibitor.

The invention relates to a core-shell structure drug-loaded magnetic-thermal hydrogel microsphere for treating drug-resistant ovarian cancer and a preparation method thereof, belonging to the field of biological and medical micro-nano materials and technologies, and the core-shell structure drug-loaded magnetic-thermal hydrogel microsphere is formed by combining an inner core and a shell layer through covalent crosslinking and electrostatic interaction. An anti-tumor drug cis-platinum and magnetic nanoparticles are loaded on an inner core, and an AZ191 inhibitor is loaded on a chitosan shell, so that preferential release of AZ191 is realized to inhibit a drug-resistant signal channel and reduce the drug resistance of cancer cells, and the cis-platinum is slowly released after the action is completed to kill tumor cells. And the magnetic nanoparticles in the inner core can be heated under an external magnetic field, so that multifunctional synergistic treatment of magnetic hyperthermia, drug resistance inhibition and chemotherapy is realized. Chitosan and sodium alginate are biodegradable materials, so that the utilization rate of the embedded medicine can be increased, and meanwhile, the medicine can be metabolized out of a body. The preparation method does not relate to toxic cross-linking agents and organic solvents, and the prepared hydrogel core-shell microspheres have no biotoxicity. Complicated operation steps are not needed, the technological process is simple, the preparation period is short, and the application range is wide.

The invention discloses application of an AI-driven target screening technology in anti-obesity treatment of a drug delivery system, and belongs to the field of cross fusion of biological medicine and artificial intelligence. The screening method provided by the invention comprises the following steps: selecting a signal channel target and active small molecules related to lipid metabolism; processing the signal channel target and the active small molecules through the data set to obtain an input matrix; and inputting the input matrix into a deep learning model to obtain the interaction intensity between the active small molecules and the signal path target. According to the method, an artificial intelligence technology is introduced, a deep learning model is constructed to efficiently predict the affinity between a drug and a protein target, the problems that a traditional target screening method depends on experience and is low in efficiency are solved, and target expression is subjected to experimental verification through a molecular biology method, so that the target screening efficiency is improved. A verification closed loop from calculation prediction to molecular demonstration is realized, and the biological credibility of a target screening result is proved.

The invention belongs to the technical field of functional nanoprobes and biological detection, and particularly relates to a kit for simultaneously detecting a specific membrane protein marker and a membrane protein dimer and application of the kit. The detection kit comprises a membrane proteome anchoring chain, a recognition probe, an SERS probe and an auxiliary signal amplification reagent, by combining DNA logic sensing based on aptamer recognition and logic response type assembly based on EpCAM protein expression and DNA signal amplification of Met protein dimerization, networked assembly of a recognition probe and an SERS probe is realized, so that specific accurate recognition of tumor cells and high-sensitivity SERS detection and imaging of membrane protein dimers are realized; the method is suitable for monitoring an HGF / Met signal channel based on Met protein dimerization mediation between stromal cells and cancer cells in a complex tumor microenvironment, and can evaluate the inhibition effect of a targeted drug on receptor dimerization in real time.

The invention relates to the technical field of immune cell culture, in particular to an immune cell culture data monitoring method and system based on activation analysis. When the immune cell culture equipment monitors that the signal protein is conducted on the abnormal standard signal channel, the real-time metabolic network is reduced based on the interference degree of the abnormal standard signal channel on the metabolic pathway, the metabolic enzyme concentration is calculated and analyzed, and a metabolic activity monitoring reference is generated; if it is monitored and detected in real time that unreasonable metabolism conditions exist in metabolic data of immune cell culture, peak integral deviation parameters for cell factor compensation are constructed based on the metabolic enzyme concentration deviation value of the metabolic activity monitoring benchmark to conduct injection compensation regulation and control on cell factors of the cultured immune cell sample. According to the method, the abnormal proliferation data, the abnormal proliferation-causing signal path data and the metabolic data in the immune cell culture process can be subjected to rapid and accurate activation analysis, so that the immune cell activation performance can be better optimized, and the culture quality is improved.

The invention relates to the technical field of traditional Chinese medicine research, in particular to a discovery method of a cough relieving and phlegm eliminating quality marker of cough relieving granules and the quality marker. According to the application, the cough-relieving and phlegm-eliminating drug effects of the cough-relieving granules are evaluated by virtue of concentrated ammonia water cough inducing and phenol red excretion tests, plasma pharmaceutical chemistry research of the cough-relieving granules is developed by virtue of a UHPLC-Q-Exactive Plus Orbitrap HRMS technology, and 26 prototype blood-entering components of the cough-relieving granules are analyzed and identified; through network pharmacological analysis of components entering blood, 11 potential active components for relieving cough and eliminating phlegm of the cough-relieving granules are screened, relate to 40 common targets such as IL6, TLR4, STAT3 and the like, and mainly participate in signal channels such as PI3K-Akt, HIF-1, EGFR (epidermal growth factor receptor) and the like; the seven prototype blood-entering components are quantitatively analyzed by utilizing pharmacokinetics. The three compounds of azelaic acid, caffeic acid and vanillin are used as the cough relieving and phlegm eliminating quality markers of the cough relieving granules through effectiveness, transitivity and testability. The research result is of great significance in deeply defining the pharmacodynamic material basis of the cough-relieving granules, optimizing the quality standard and promoting the clinical application of the cough-relieving granules.

The invention relates to the technical field of biology, in particular to application of a rice OsPBL8 gene in enhancing resistance of rice to magnaporthe oryzae. The rice OsPBL8 gene is a rice endogenous gene participating in the processes of plant growth and development, abiotic stress response, hormone signal channel regulation and control and the like. The invention provides application of the OsPBL8 gene in the field of disease resistance, the OsPBL8 gene is overexpressed through gene editing, and the expression quantity of receptor-like cytoplasm kinase OsPBL8 in plants is increased, so that a plurality of signal channels are regulated and controlled, and the germ resistance of the plants is synergistically improved. By adjusting key hub nodes of plant targeted immune signal transduction, more lasting broad-spectrum disease resistance can be provided, good universality is achieved, disease resistance and growth can be balanced, good practicability is achieved, and improvement of disease resistance of various rice varieties is facilitated.

The invention discloses application of LECT2 as a diagnosis and treatment target of hepatic ischemia reperfusion injury. According to the present invention, the Print method operation patient sample is detected to discover that the expression of the LECT2 in the hepatic ischemia reperfusion injury is up-regulated; on the basis, a liver ischemia reperfusion injury model is constructed by knocking out a mouse through the LECT2 gene, and a result shows that the liver ischemia reperfusion injury of the mouse is obviously reduced by knocking out the LECT2 gene and transferring the LECT2-shRNA into the LECT2 gene, and the liver ischemia reperfusion injury of the mouse is aggravated by LECT2 recombinant protein; it is shown that inhibition of expression of LECT2 is beneficial to improvement or treatment of hepatic ischemia injury; furthermore, the invention further finds that liver injury can be relieved by inhibiting the combination of LECT2 and Tie1; the LECT2 / Tie1 signal channel can also be used as a target spot for treating the liver ischemia reperfusion injury.

The invention provides application of dsRNA in inhibition of reproductive capacity of bemisia tabaci, and belongs to the technical field of pesticides. The dsRNA is one or more of dsBtInR1 and dsBtInR2, and the dsRNA is one or more of dsBtInR1 and dsBtInR2. According to the invention, two bemisia tabaci insulin receptor genes BtInR1 and BtInR2 are found, and after the expression levels of BtInR1 and BtInR2 in bemisia tabaci are knocked down, a JH signal channel can be influenced by interfering an insulin signal channel, and finally, the reproductive capacity of the bemisia tabaci is inhibited, so that a theoretical and application basis is provided for developing and producing green biopesticide for preventing and treating the bemisia tabaci.

The invention discloses a VEGF / TIE-2 dual-targeting polypeptide and application thereof in preparation of antitumor drugs, and relates to the technical field of biological medicines. The VEGF / TIE-2 dual-targeting polypeptide (named as RTP) provided by the invention is formed by combining an amino acid sequence capable of identifying VEGF and TIE-2 in a targeting manner, an amino acid sequence capable of forming beta-sheet nanofibers through self-assembly, an amino acid sequence capable of identifying carbonic anhydrase IX in a targeting manner and an enzyme reactive amino acid sequence capable of realizing MMP-2 specific shearing. The RTP can be subjected to allosteric and self-assembly in tumor cells to form stable water-insoluble nanofibers, the formation and metastasis of tumor neovascularization are strongly inhibited through VEGF and TIE-2 double signal channels, and the tumor progress is inhibited.

The invention discloses a double-target chimeric antigen receptor for co-expression of CD47 and IL-15, a CAR-T cell and application of the CAR-T cell, and belongs to the technical field of genetic engineering, the double-target chimeric antigen receptor comprises a single-chain antibody scFv-EGFRv III, a single-chain antibody scFv-VEGF, CD47 and IL-15; the nucleotide artificial sequence of the single-chain antibody scFv-EGFRv III is as shown in SEQ ID NO. 6; the nucleotide artificial sequence of the single-chain antibody scFv-VEGF is as shown in SEQ ID NO. 9. According to the application disclosed by the invention, by performing sequence optimization on targets EGFRvIII and VEGF, the anti-tumor effect of CAR-T cells in glioblastoma can be improved, and by integrating immune checkpoint molecules CD47 and interleukin-15, the immunosuppression function of a CD47-SIRP alpha signal channel can be locally exerted.

The invention belongs to the technical field of biotechnology and botany, and particularly relates to a small peptide for improving abiotic stress tolerance of crops and application of the small peptide, and the small peptide is GhIDL02 and / or GhPIPL7. The amino acid sequence of the GhIDL02 is as shown in SEQ ID NO. 1; the amino acid sequence of the GhPIPL7 is as shown in SEQ ID NO. 2. According to the method, the small peptide GhIDL02 or GhPIPL7 is exogenously applied, so that the hormone-like effect is quickly exerted, the salt tolerance of the cotton is remarkably improved, and the adverse effect of a chemical regulating agent on the environment is avoided. Through a research technology combining bioinformatics and molecular biology, the positive regulation effect of the GhIDL02 and GhPIPL7 small peptides under salt stress is confirmed for the first time, and by activating an MAPK signal channel, the steady state of cotton sodium and potassium ions is maintained, the salt tolerance of cotton is improved, and a theoretical basis and technical support are provided for green development of an agricultural biotechnology.

The invention discloses a chimera for degrading a CARD structural domain protein aggregate and application of the chimera. The chimera is prepared from light-operated targeting protein and light-operated degradation protein, the light-operated targeting protein is sequentially connected by an MAVS CARD structural domain, a flexible connecting peptide and a photosensitive protein pMag; the light-controlled degradation protein is sequentially connected by a photosensitive protein nMag, a flexible connecting peptide and an RING structural domain of TRIM21. According to the application, a light-operated activated CARD-RING chimera is constructed, and when the CARTAC generates toxic and side effects or in cells with RIG-I / MDA5 signal channels abnormally activated, the activity of the CARTAC can be effectively controlled or autoimmune diseases caused by RIG-I / MDA5 abnormity can be inhibited.

The invention relates to the technical field of strategy optimization, in particular to an ASIC (Application Specific Integrated Circuit) layout optimization method based on hybrid shaping programming, which comprises the following steps of: analyzing a circuit netlist, and establishing a signal path physical model containing static topological connectivity; a candidate layout scheme is generated based on the model, and layout state data describing the state of the candidate layout scheme is generated through physical effect simulation; based on the layout state data, calculating a signal processing performance index and a wiring cost value, and generating a group of dynamic shaping constraints for guiding subsequent layout according to the index and the cost value, the dynamic shaping constraints being quantitative adjustment of a path congestion perception graph in a signal path physical model; and updating the model through the constraint, evaluating the stability of a Pareto optimal boundary formed by the performance index and the cost value so as to judge convergence, and finally outputting a layout scheme associated with a stable state. According to the method, dynamic shaping constraints are generated through a strategy optimization algorithm, and global collaborative optimization of multiple targets such as time sequence and wiring performance is achieved.

The invention belongs to the technical field of protein, and relates to a peptide with liver protection activity and a preparation method and application thereof, and the amino acid sequence of the peptide is PFPRPQP. The active peptide can be used for activating a Keap1 / Nrf2 signal channel by reducing the liver enzyme level and inhibiting CYP2E1 expression so as to play a role in protecting HepG2 damaged cells. The invention also provides a preparation method and application of the liver-protecting active peptide.

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition, a preparation method thereof and application of the traditional Chinese medicine composition in preparation of medicines for preventing and treating stress insomnia. The composition provided by the invention is composed of vinegar-processed rhizoma cyperi, green tangerine peel, pinellia ternate, poria with hostwood, salvia miltiorrhiza, ginseng, rhizoma acori graminei, nacre mother of pearl, crude dragon bone and ginger, and the comprehensive advantages of the composition in treatment of stress insomnia are shown through a multi-target and multi-channel regulation mechanism in combination with significant regulation effects of GO function enrichment and KEGG signal channels. The multi-layer action mechanism provides a unique treatment potential for the formula, and particularly has an important clinical application prospect in the aspect of coping with complex stress response and nerve dysfunction.

The invention discloses an engineered NK cell and a preparation method thereof. The antitumor activity of the NK cell is enhanced through synergistic modification of a fusion polypeptide and an anti-TIGIT monoclonal antibody. The amino acid sequence of the fusion polypeptide is shown as SEQ ID NO.1. The fusion polypeptide can specifically target tumor cells and activate the proliferation and killing functions of NK cells. And the anti-TIGIT monoclonal antibody further relieves the immunosuppression by blocking a TIGIT-CD155 signal channel. In-vitro experiments show that the killing rate of the combined modified NK cell on various solid tumors is obviously higher than that of the traditional CAR-NK cell. A PDX model shows that the engineered NK cells significantly inhibit tumor growth and enhance NK cell infiltration in a tumor microenvironment. The invention provides a new strategy with high efficiency and low toxicity for immunotherapy of solid tumors.

The present disclosure relates to 3-substituted 1,2,4-oxadiazole compounds and their derivatives, which are useful as V-domain immunoglobulin suppressor of T-cell activation (VISTA) inhibitors or as dual inhibitors of VISTA and the programmed cell death 1 (PD-1) signaling pathway. The disclosure also relates to treatment of disorders by inhibiting an immunosuppressive signal induced by VISTA and its ligands, PD-1, PD-L1, and / or PD-L2.

The invention relates to application of a cGAS-STING signal channel inhibitor in preparation of a product for preventing or treating abdominal adhesion, and belongs to the technical field of biological medicines. The invention finds that peritoneal dialysis causes that a peritoneal mesothelial cell cGAS-STING pathway and downstream protein thereof are activated, inflammatory factors are generated, and the peritoneal mesothelial cell secretes a chemotactic factor CCL2 (MCP-1) participating in macrophage recruitment, so that migration of macrophages can be promoted, and abdominal adhesion is caused. The cGAS-STING signaling pathway inhibitor can be used for relieving the effects, so that the aim of treating abdominal adhesion is fulfilled.

The invention relates to the technical field of biology, in particular to a tumor postoperative vaccine as well as a preparation method and application thereof. The method comprises the following steps: resuspending tumor cells in a first solution containing metal ions for incubation, collecting the tumor cells, resuspending the tumor cells in a second solution containing mineralized ions for incubation, enabling the metal ions to react with the mineralized ions to obtain metal inorganic salt, forming a mineralized shell layer on the surfaces of the tumor cells, and resuspending the tumor cells to obtain the tumor postoperative vaccine. And due to the mineralized shell layer, the vaccine has the capability of activating a signal channel in an antigen presenting cell through mechanical stimulation, so that an immune system is favorably activated, and the anti-tumor capability of the vaccine is improved. In addition, tumor cells are inactivated in the vaccine preparation process and keep a complete form, and presentation of a complete tumor antigen is facilitated, so that a relatively good anti-tumor effect is obtained.

The invention relates to the technical field of biology, in particular to application of YAP related protein in intestinal ischemia-reperfusion lung injury. The application comprises the application of the overexpressed YAP related protein 1 in treating or inhibiting the intestinal ischemia-reperfusion lung injury; based on the regulation and control effect of a transcriptional regulatory factor of the YAP-associated protein 1 in a Hippo-YAP signal channel, accumulation of overexpressed YAP-associated protein 1 in a cell nucleus is used, so that a large amount of YAP-associated protein 1 is overexpressed in the cell nucleus, expression of downstream Nrf2 genes in the cell nucleus and transfer of the YAP-associated protein 1 in the cell nucleus can be regulated and controlled, and the YAP-associated protein 1 can be expressed in the cell nucleus. According to the present invention, the overexpressed YAP-associated protein 1 can be used to inhibit ferroptosis of intestinal ischemia-reperfusion lung injury tissues, and the overexpressed YAP-associated protein 1 can be used to improve lung injury, such that the overexpressed YAP-associated protein 1 can be used to protect lung epithelium injury caused by intestinal ischemia-reperfusion.

The invention relates to a method for enhancing target cell removal capacity of immune cells and application. The method comprises the following steps: recombining CD58 and TP53 genes with a granzyme B gene so as to obtain recombinant genes NFAT-GZMB-CD58 and NFAT-GZMB-TP53, and meanwhile, adding a transcription factor NFAT binding site into a regulation region of the obtained recombinant genes. Then, the two recombinant genes are directionally inserted into specific gene loci of immune cells through a gene editing technology. Expression of the two recombinant genes is regulated and controlled by an immune cell activation signal pathway, and translation products of the two recombinant genes can be delivered to target cells of immune cells through a granzyme-perforin pathway, so that the scavenging capacity of the immune cells to the target cells is enhanced, and apoptosis and escape of the target cells are inhibited. The method can be applied to the field of cell therapy.

The present disclosure relates to 3-substituted 1,2,4-oxadiazole compounds and their derivatives, which are useful as T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) inhibitors or as dual inhibitors of TIM-3 and the programmed cell death 1 (PD-1) signaling pathway. The disclosure also relates to treatment of disorders by inhibiting an immunosuppressive signal induced by TIM-3, PD-1, PD-L1, and / or PD-L2.

The invention discloses an MMP2 gene promoter region SNP (Single Nucleotide Polymorphism) site and application thereof in pig breeding. According to the invention, an MMP2 gene promoter region is taken as a research object, and the relevance between the MMP2 gene promoter region and sow sexual maturity is researched by adopting a molecular and cell biology method, so that the situation that g.30088284G > A site and g.30088004C > T site are obviously related to the group maturity day age of Dumet black pigs is found; then different vectors are transfected, and different influences of different genotypes of the sites on the activity of the IRS1 gene promoter are studied. Further, sow ovarian granular cells are used as experimental materials, experimental technologies such as transcriptome sequencing, a total iron colorimetric method and a malondialdehyde colorimetric method are adopted, the influence of the MMP2 gene on the transcriptome level and ferroptosis of the sow ovarian granular cells is researched, and it is found that cell transcriptome differential genes influenced by the MMP2 gene are mainly enriched to signal channels such as cell differentiation; and ferroptosis of cells is promoted.

The invention relates to the technical field of biology, and particularly discloses a polypeptide and application thereof in enhancing immunity and / or resisting inflammation. The invention provides a polypeptide. The amino acid sequence of the polypeptide is shown as SEQ ID NO. 1. The compound has the dual functions of regulating immunity and resisting inflammation, on one hand, the immune function of cells under the normal condition can be enhanced, and on the other hand, cell inflammation can be relieved by reducing the phosphorylation level of key protein in an LTR4-NF-kappa B signal channel in the inflammatory state. The polypeptide is low in cytotoxicity, high in safety, simple in preparation method and low in cost, can be used as an ideal immune and anti-inflammatory regulator, and has good application potential and value.

The invention discloses a DCS system IO module channel testing device, and relates to the technical field of industrial automation equipment detection. The device comprises an IO module point inspection instrument and an upper computer, the IO module point inspection instrument is in communication connection with the upper computer, a plurality of sets of independent test modules capable of running in parallel are arranged in the IO module point inspection instrument, and each test module comprises a controller, an excitation source circuit, a signal acquisition circuit and a matrix switch circuit and corresponds to one slot. And the test module establishes a signal path with the IO module connected to the slot through the matrix switch circuit. Wherein a controller in the test module can automatically identify the type of the IO module to be tested, dynamically configure an excitation source circuit and a signal acquisition circuit which are matched with the IO module to be tested, and realize automatic and high-precision detection of various types of IO modules. According to the device, the point inspection efficiency of the IO module of the DCS system can be greatly improved by integrating a multi-channel signal output function and a signal detection function.