265 results about "Caspase" patented technology

The invention belongs to the field of biological medicines, and particularly discloses application of a Ptprj agonist GJ103 in preparation of a medicine for treating acute kidney injury (AKI) induced by cisplatin. In-vivo and in-vitro experiments prove that the GJ103, by activating Ptprj, can significantly down-regulate expression of pro-apoptotic protein Bax and Cleved Caspase-3, up-regulate anti-apoptotic protein Bcl2 and reduce infiltration of inflammatory factors TNF-alpha and IL-6, so that apoptosis and inflammatory response of renal tubular epithelial cells are relieved. In in-vivo experiments, GJ103 (20-40mg / kg / day) can reduce serum creatinine and urea nitrogen levels of cis-platinum model mice and improve pathological injuries such as renal tubule dilatation; in in-vitro experiments, 20-40 [mu] M of GJ103 can inhibit apoptosis of renal tubular epithelial cells and reduce expression of renal injury markers NGAL and Kim-1. The pharmaceutical composition contains GJ103 and a pharmaceutical carrier, the preparation form can be a 4mg / mL injection (the purity is greater than or equal to 99.46%) or an oral preparation, and a new strategy is provided for clinical treatment of cisplatin renal toxicity.

The invention relates to application of 12-ketolithocholic acid in preparation of a medicine for preventing or treating acute ischemic intestinal injury. According to the application, 12-ketolithocholic acid (12-KLCA) is used for preventing or treating acute ischemic intestinal injury and is verified on a constructed classical intestinal ischemia reperfusion model, and a verification result shows that the 12-KLCA obviously improves intestinal histopathologic injury induced by intestinal ischemia reperfusion of a mouse, improves the survival rate of the mouse, and has a good application prospect in prevention or treatment of acute ischemic intestinal injury. The protein expression level of the apoptosis factor activated caspase-3 is reduced, the effect is obvious, safety and non-toxicity are achieved, and the side effect is small.

The invention discloses a method, a system and equipment for evaluating the treatment effect of PTT on pancreatic cancer. According to the application disclosed by the invention, PTT is found to treat pancreatic cancer by regulating a caspase-1 / GSDMD pathway for the first time, and the expression level of GSDMD is found to be in positive correlation with the drug resistance of pancreatic cancer cells to 5-fluorouracil, irinotecan, paclitaxel and cis-platinum, which prompts that people can adopt a local treatment method of photothermal therapy instead of traditional chemotherapy for patients with high expression of GSDMD. Besides, the invention provides a method, a system and equipment for evaluating the treatment effect of PTT on pancreatic cancer and a method, a system and equipment for predicting the sensitivity of pancreatic cancer patients to chemotherapeutics, thereby assisting doctors in evaluating the treatment effect of pancreatic cancer patients and guiding clinicians to formulate individualized treatment schemes for patients.

Aspects of the disclosure relate to Botulinum toxin X (BoNT X) protein variants. The variants provided herein have been evolved to cleave GTP cyclohydrolase 1 (GCH1). Some of the variants provided herein were evolved from a procaspase-1 cleaving polypeptide. Further aspects of the disclosure relate to nucleic acids encoding the GCH1 cleaving polypeptides described herein and expression vectors comprising the nucleic acids, as well as host cells and fusion proteins comprising the GCH1 cleaving polypeptides described herein, and kits comprising the GCH1 polypeptides, fusion proteins, nucleic acids, expression vectors, or host cells described herein. Further aspects of the disclosure relate to methods of producing BoNT X variants and methods of using the BoNT X protein variants, for example, to reduce pain.

The invention discloses design and synthesis of a series of brain-targeted ginsenoside Rg1 derivatives and application of the brain-targeted ginsenoside Rg1 derivatives in treatment of Alzheimer's disease. According to the invention, ginsenoside Rg1 and polyethylene glycol with a specific chain length are covalently linked to successfully construct the derivative capable of enhancing the penetrating power of the blood-brain barrier. The series of derivatives provided by the invention not only solve the problems of poor brain targeting and insufficient stability of natural Rg1, but also can inhibit neuroinflammation by regulating and controlling an NLRP3 / caspase-1 signal channel in an LPS-induced neuroinflammation model, and finally, the learning and memory ability is remarkably improved. The product is simple and convenient in preparation process and good in biological safety, and a new candidate compound is provided for developing a new generation of Alzheimer disease treatment medicines.

The invention relates to the technical field of antitumor drugs, in particular to a cyclometalated iridium (III) complex as well as a preparation method and application thereof. The cyclometalated iridium (III) complex has a structure as shown in a formula I which is described in the specification. Experimental results show that the cyclometalated iridium complex provided by the invention has excellent anti-tumor activity, can enter tumor cells in an energy-dependent manner, and gathers on endoplasmic reticulum and lysosome. Caspase-1 can be activated to induce cells to generate a large amount of ROS, the cells are further induced to generate pyroptosis by activating the Caspase-1, and a large amount of inflammatory factors are released. In in-vitro experiments, migration of tumor cells can be effectively inhibited. In further in-vivo experiments, the cyclometalated iridium complex can influence normal development of zebrafish embryo blood vessels to different degrees. The cyclometalated iridium complex provided by the invention can induce tumor cell death by inhibiting angiogenesis.

The disclosure provides inducible caspase polypeptides, compositions comprising inducible caspase polypeptides and sequences encoding the same, cells modified to express the polypeptides and compositions of the disclosure, as well as methods of making and methods of using same for adoptive cell therapy.

The invention provides a method for detecting the influence of drug-containing serum of Sijunzi decoction on hepatic stem cells. The method comprises the steps of cell culture, drug-containing serum preparation, cell proliferation experiment, cell damage model establishment and treatment, oxidative stress related index detection, protein expression analysis and the like. According to the method, cell activity is detected through a CCK-8 method, cell nucleus morphological change is observed through Hoechst 33342 staining, the apoptosis rate is detected through Annexin V / PI double staining in combination with flow cytometry, apoptosis-related protein expression is detected through Western blot, and the action mechanism of the drug-containing serum is comprehensively evaluated. Experimental results show that the drug serum of the Sijunzi decoction can promote proliferation of liver stem cells, reduce oxidative stress injury induced by H2O2, improve cell viability and oxidation resistance, reduce cell apoptosis rate, up-regulate expression of anti-apoptotic protein Bcl-2 and inhibit expression of pro-apoptotic protein Bax and Cleaved Caspase-3 at the same time.

The invention belongs to the technical field of biomedicine, and provides application of inhibition of Caspase-8 expression in preparation of a medicine for improving macrophage pan-apoptosis. The invention also discloses an application of the NLK gene in preparation of a medicine for improving Caspase-8 dependent macrophage pan apoptosis. In-vitro experiments prove that under the state of sepsis, up-regulated NLK can regulate and control generation of Caspase-8-dependent macrophage pan apoptosis through protein interaction; through NLK knockout, the occurrence of Caspase-8 dependent pan apoptosis can be inhibited, and the death of macrophages is effectively reduced. Therefore, the research results show that the target regulation of Caspase-8-dependent pan apoptosis by intervening the NLK gene is expected to provide benefits for the treatment of sepsis; and a new method is provided for clinical treatment of sepsis.

The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors. These data suggest the generality of drug-mediated MEK kinase cleavage as a therapeutic strategy to prevent resistance to targeted anticancer therapies.

To develop a novel plant extract having an excellent skin-conditioning effect.SOLUTION: Provided are a caspase-14 activator or an anti-oxidizing agent containing a Japanese apricot extract, and an external preparation for skin containing the caspase-14 activator or the anti-oxidizing agent.EFFECT OF THE INVENTION: According to the present invention, skin is protected from dryness, ultraviolet light and active oxygen which are harmful to skin by increasing the enzymatic activity of caspase-14 and deleting active oxygen, and a skin-conditioning effect that the external preparation for skin should include can be realized.SELECTED DRAWING: Figure 1

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3

This invention discloses the application of the inflammasome NLRP6 as a target in screening drugs for treating epilepsy, and the application of NLRP6 expression inhibitors in the preparation of drugs for treating epilepsy. This invention reveals for the first time the role of the inflammasome NLRP6 in epileptic neuroinflammation. This invention identifies NLRP6 as a key regulator of neuroinflammation in epilepsy and investigates its role in activating the caspase-1 / IL-1β / IL-18 signaling pathway. Knockdown of NLRP6 can improve the damaging effects of epilepsy on neurons, thereby improving seizures; overexpression of NLRP6 may exacerbate seizures, neuronal damage, and neuroinflammatory responses. This invention provides a new potential target for epilepsy treatment, offering new research ideas and directions.

The present invention provides a cryoprotective additive for human sperm and a preparation method thereof. The method is to add an mTORC1 activator and a Caspase-9 inhibitor to a commercially available sperm cryoprotectant. Compared with the pure commercially available protectant, the cryoprotective additive of the present invention has an increased number of forward-moving sperm after thawing and recovery; there are more forward-moving sperm after recovery, with better forward motility and better forward motility endurance. At the same time, the mitochondrial structure and function of the sperm cells after recovery are less damaged, the mitochondrial function recovers quickly, less mitochondrial ROS is produced, apoptosis is reduced, the ability to protect the function of sperm cells is better, and it is more conducive to the long-term cryopreservation of sperm-like cells.

The application discloses application of a pyrimidinotriazine diketone derivative in preparation of a medicine for inhibiting activity of human protease caspase-1, and belongs to the technical field of medicines. In view of defects of existing caspase-1 inhibitors, the compound has the characteristics of high affinity binding to caspase-1 (K D = 8.11 μM; 8.78 μM) and strong inhibition on the activity (IC 50 = 11.90 nM-14.47 nM). The compound is used for preparation of a medicine for inhibiting the activity of caspase-1 and a medicine for treating inflammation-related diseases such as sepsis-related lung injury, acute respiratory distress syndrome or acute pancreatitis.

To provide immunoresponsive cells having IL-1 superfamily activities with spatiotemporal restriction.SOLUTION: The present invention provides an immunoresponsive cell expressing a modified pro-cytokine of the IL-1 superfamily, where the modified pro-cytokine comprises, from N-terminus to C-terminus, (a) a pro-peptide; (b) a cleavage site recognized by a protease other than caspase-1, cathepsin G, elastase or proteinase 3; and (c) a fragment of a cytokine of the IL-1 superfamily.SELECTED DRAWING: None

The present invention relates to the field of biomedicine technology, and discloses a use of melanin in the preparation of a drug for treating chronic ulcerative colitis and its associated depressive-like behavior. The present invention is the first to discover that melanin has the efficacy of treating chronic ulcerative colitis and its associated depressive-like behavior. MSPI can inhibit the LPS / TLR4 / NLRP3 / ASC / Caspase‑1 inflammatory signaling pathway, reduce oxidative stress, and restore the intestinal barrier, thereby improving UC symptoms. In addition, MSPI can also reduce glial cell activation, brain neuroinflammatory response and neuronal apoptosis, thereby reducing depressive-like behavior.

The invention discloses an application of a coix seed extract in preparation of a medicine for preventing and treating acute lung injury. The semen coicis extract is obtained by performing reflux extraction on semen coicis by using ethanol, recovering an extraction solvent by using a rotary evaporator and then performing evaporation concentration by using a water bath. The coix seed extract can obviously increase the thymus index, improve the pathological injury of lung tissues, reduce the level of inflammatory factors in serum and lung tissues, possibly inhibit the expression of NLRP3, Caspase-1 and GSDMD-N in NLRP3 signal channel key proteins in the lung tissues, inhibit the NLRP3 signal channel, inhibit inflammation and pyroptosis, and play a role in protecting ALI. The coix seed extract can inhibit the activation of an NLRP3 signal channel and play a role in treating the acute lung injury disease.

The invention provides a diagnosis and treatment integrated nano platform as well as a preparation method and application thereof. According to the diagnosis and treatment integrated nano platform, an organic-inorganic nano hybrid is constructed through structure optimization and function integration, four modes of PTT, PDT, SDT and CDT are organically combined innovatively, and efficient synergistic treatment of GBM is achieved through real-time monitoring of photoacoustic imaging. First, a dOMV encapsulation strategy significantly improves the ability to penetrate through the blood brain barrier. Meanwhile, the IEICO-4F has a strong near-infrared absorption characteristic and has a synergistic effect with the high catalytic activity of the mesoporous platinum nanoparticles. Under the laser / ultrasonic excitation condition, the diagnosis and treatment integrated nano platform shows excellent photo-thermal conversion performance, the Fenton reaction rate can be increased, endogenous hydrogen peroxide can be continuously catalyzed to be decomposed to generate oxygen, and the tumor hypoxia state is effectively relieved. The series of reactions further enhance the generation of ROS, activate a Caspase-1 / GSDMD mediated pyroptosis pathway, finally achieve an efficient tumor inhibition effect, and successfully break through the limitation of a single treatment mode.

The present application belongs to the technical field of hair loss treatment, and particularly relates to a phototherapy and drug synergistic intervention system for androgenetic alopecia of human scalp. In the system, the drug is angelica extract with a concentration of 0.1-500 ug / mL; the phototherapy light source is a red light LED light source with a wavelength of 600-700 nm; the light irradiance is 2-100 mW / cm 2 ; the light dose is 2-20 J / cm 2 ; the irradiation mode is steady light or pulsed light; and the synergistic intervention mode is that the phototherapy and the drug application are performed synchronously or the phototherapy is performed within 0.5-2 hours after the drug application. Experiments show that the light-drug combined intervention significantly improves cell viability, ATP level, migration ability, IGF1 and VEGF secretion, reduces ROS and MDA levels, inhibits Caspase-3 activity, regulates BCL2 / BAX expression, activates Wnt, Hh and PI3K pathways, and inhibits BMP and TGF-beta pathways. The present application provides a treatment scheme with clear timing and standardization, and realizes safe, non-invasive and efficient hair loss treatment.

The invention discloses a preparation rich in polygonatum sibiricum polypeptide and application of the preparation in diabetes mellitus. The composition is prepared from rhizoma polygonati polypeptide, semeglutide, astaxanthin, an active agent and a ferroptosis mixture. Pharmacodynamic experiments show that in a diabetic mouse model, fasting blood glucose can be remarkably reduced, the serum insulin level can be increased, renal function indexes can be improved, and expression of NLRP3 inflammation pathway related proteins (NLRP3, Caspase-1 and IL-1beta) in pancreatic tissue can be remarkably inhibited. By integrating multiple mechanisms of blood glucose reduction, oxidation resistance, inflammation resistance, ferroptosis resistance and the like, multi-target collaborative intervention is realized, the pharmaceutical composition is remarkably superior to a single component in the aspects of blood glucose reduction, pancreas islet function protection and complication alleviation, and a new clinical strategy is provided for treatment of diabetes mellitus, especially type 1 diabetes mellitus.

The invention provides medical application of a licochalcone B derivative CTG12 in preparation of an NLRP3 inflammasome inhibitor, and belongs to the technical field of biological medicine. The invention provides application of a licochalcone B derivative CTG12 in preparation of an NLRP3 inflammasome inhibitor. The invention also discloses application of the compound in preparation of drugs for preventing or treating diseases related to abnormal activation of NLRP3 inflammasomes. The synthesized compound CTG12 has the remarkable activity of inhibiting caspase-1 generated by BMDM cells, the effect is improved by about eight times compared with licochalcone B, and the compound CTG12 has the broad-spectrum and specific inhibiting effect and can effectively inhibit activation of NLRP3 inflammasomes.

The invention discloses application of TPN171H, an active fragment thereof or a derivative thereof in preparation of a medicine for treating spinal cord injury. The TPN171H shows an excellent treatment effect in spinal cord injury treatment, the levels of apoptosis factors BAX and Caspase-3 cleaved can be remarkably reduced, the level of Bcl-2 is improved, the content of a neuron marker MAP-2 is also remarkably increased, and the number of Tunel bodies and the cavitation-like structure are remarkably reduced. The intervention of the TPN171H also can reduce MNSS, and prompts that the TPN171H has the functions of promoting the spinal cord movement and coordination of the rat with spinal cord injury and improving the sensory system of the rat with spinal cord injury.

The present invention relates to a preparation method of a manganese tetraoxide / GSDME complex and its application, which can effectively solve the problem of tumor cell re-proliferation and normal tissue damage after radiotherapy. The technical solution is to firstly prepare a manganese tetraoxide / GSDME complex in the presence of Mn 3 O 4 The surface of the nanoparticles is modified with GSDME protein, and a manganese tetraoxide / GSDME complex is prepared by cross-linking tannic acid with the GSDME protein. The preparation method of the invention is stable and reliable, and is easy to operate. 3 O 4 The / GSDME complex has the advantages of good biocompatibility and low toxicity and side effects. It can achieve efficient intracellular delivery of GSDME protein, activate the Caspase-3 / GSDME signaling pathway, convert radiotherapy-induced tumor cell apoptosis into pyroptosis to inhibit tumor regeneration; and utilize the difference in intracellular GSH content between tumor cells and normal cells to inhibit the expression of Mn in tumor cells. 3 O 4 It can enhance radiosensitization by downregulating GSH, while Mn 3 O 4 It is an innovation in tumor radiotherapy drugs to exert its nanozyme activity to eliminate ROS produced by radiotherapy and achieve radiation protection for normal tissues.

The present invention discloses an application of a medicated serum prepared from Herba Lycopodii in liver cancer cells, and belongs to the field of medical technology. The present invention provides a medicated serum prepared from Herba Lycopodii in the preparation of a drug for inhibiting the proliferation and invasion of liver cancer cells, and promoting apoptosis of liver cancer cells. The present invention verifies that the Herba Lycopodii medicated serum can effectively inhibit the proliferation and invasion of HepG2 cells, promote cell apoptosis, and inhibit the phosphorylation of mTOR protein in the mTOR signaling pathway of HepG2 cells, upregulate the expression of pro-apoptotic proteins caspase-9, caspase-3, and bax, and downregulate the expression of anti-apoptotic protein bcl-2. The present invention studies the effects of the Herba Lycopodii medicated serum on related apoptosis genes in the mTOR molecular signaling pathway of HepG2 liver cancer cells and the proliferation, invasion, and apoptosis of HepG2 liver cancer cells from the perspective of in vitro experiments, in order to provide an experimental basis for clinical application.

The invention belongs to the technical field of pathogenic bacteria detection, and discloses an amplification-free microbial molecule detection method and a detection kit based on Caspase (Cas7-11-crRNA-Csx29) / SNLuc-Csx30 (Splitt NanoLuc-Csx30). The detection method comprises the following steps: carrying out amplification on the Caspase (Cas7-11-crRNA-Csx29); the kit comprises a Crapase protein nucleic acid compound, an SNLuc-Csx30 protein, a Furimazine molecule, a Crapase protein nucleic acid compound, a Crapase protein nucleic acid compound and a Crapase protein nucleic acid compound, wherein the Caspase protein nucleic acid compound is composed of Cas7-11 protein, crRNA and Csx29 protein, the crRNA sequence is guide RNA of the Cas7-11 protein, the crRNA sequence comprises a fixed sequence and a binding sequence, the binding sequence is 25nt capable of being complementary with RNA of pathogenic bacteria, the binding sequence is located at 3'of the fixed sequence, and the sequence is shown as SEQ ID NO.1; the SNLuc-Csx30 protein is a hydrolysis substrate of the Csx29 protein; the Frimazine molecule is a catalytic substrate of the SNLuc-Csx30 protein, and the Frimazine molecule is an amino acid sequence shown in the description. The kit does not need to amplify pathogenic nucleic acid in the detection process, the detection method is high in specificity and sensitivity, and the lowest detection limit can reach 1 ng / mu L.

The invention discloses a method for indicating fish freshness change by adopting cell apoptosis signal molecules and application, and belongs to the technical field of grass carp freshness detection. The invention discloses a method for indicating fish freshness change by adopting cell apoptosis signal molecules, which comprises the following steps: according to the detected contents of cell apoptosis signal molecules Caspase-3, Bax, Bcl-2 and Cyt-c, establishing a corresponding relation model between the content of the cell apoptosis signal molecules and the freshness of grass carp. According to the method, the freshness of the grass carp can be quickly and accurately judged, and a scientific basis is provided for quality control and market supervision of the grass carp. The method can be popularized and applied in actual production and market supervision.

The present application belongs to the technical field of coordination chemistry and biomedical science, and provides a multifunctional iridium (III) complex, a preparation method and application thereof. The multifunctional iridium (III) complex (Mito-Ir) is composed of an iridium (III) complex cation and a coordination anion shown in the following formula. Mito-Ir can efficiently target mitochondria, and also has the abilities of phosphorescence imaging, type I and type II active oxygen generation, and photocatalytic oxidation of nicotinamide adenine dinucleotide. Under light irradiation, Mito-Ir triggers severe mitochondrial dysfunction through the above synergistic effect, and then specifically activates the caspase-3 / GSDME signaling pathway, and significantly induces pyroptosis; this pyroptosis-based cell death mechanism can effectively overcome the apoptosis tolerance of tumor cells, and is accompanied by the release of a large amount of inflammatory factors and damage-associated molecular patterns, stimulates immunogenic cell death, and activates the body's anti-tumor immune response.

The present disclosure relates generally to alkyne containing pharmaceutical agents, and in particular, to phenylethynyl-thiophene based compounds. More particularly, the present disclosure provides a class of compounds that can inhibit and / or attenuate apoptosis via caspase 3 for the treatment of various degenerative disorders. Additionally, the present disclosure relates to methods for treating specific degenerative disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, epilepsy, spinal cord injury, complication due to diabetes, multiple sclerosis (MS), muscular dystrophy (MD), Parkinson's disease (PD), irritable bowel syndrome (IBS) and Alzheimer's disease (AD) in a patient comprising administering to the patient an effective amount of a present compound.

The present invention discloses a Caspase-3 enzyme-responsive self-assembly probe and a synthesis method and application thereof. The magnetic resonance signal of the probe of the present invention is weak in normal tissue because the probe is a small molecule compound when it does not respond to Caspase-3. 1 The H-MRI signal is weak, while 19 The F-MRI signal is shielded due to the paramagnetic relaxation enhancement effect. After the probe responds to Caspase-3, the DEVD sequence in the probe molecule will be cut off, thereby releasing two molecules, including CF3DEVD molecules and FFFK-GdDO3A molecules. The fluorine signal of the CF3DEVD molecule will be restored due to the disappearance of the shielding effect, while the FFFK-GdDO3A molecule will undergo intermolecular self-assembly due to the hydrophilic-hydrophobic effect, which will enhance the relaxation of the GdDO3A part, thereby achieving a double change in the magnetic resonance signal.