The invention relates to compositions and methods for making and use of a real-time cellular sensor. Components of a multipart enzyme are sequestered in different cellular compartments and only come together after receptor activation; a pool of substrate is made available in the cell to ensure real-time enzymatic output.

The present invention discloses an application of a β3 adrenergic receptor (ADRB3) as a marker for detecting a plurality of diseases, and an application of anti-human ADRB3 monoclonal antibody in diagnosing a disease and preparing a drug for treating the disease. The present invention finds through research that the ADRB3 is a key receptor in nerve-endocrine-immunoregulatory network, and an ADRB3-mediated signaling pathway regulates proliferation and differentiation of neutrophils, lymphocytes and tumor cells. Under normal circumstances, the ADRB3 maintains the non-specific immunocompetence and specific immunocompetence of an organism, and eliminates pathogenic microorganisms and aged organism tissues to play a role in protecting the organism and anti-aging. Under pathological conditions, excessive activation of the signaling pathway will cause systemic chronic inflammation, and destroy immune homeostasis. Therefore, the ADRB3 can be used as a diagnostic marker and a therapeutic target for a plurality of diseases. Anti-human ADRB3 antibody can specifically bond with the ADRB3, regulate the activity of the ADRB3, has the functions of resisting cancer, inflammation, poisoning, shock, allergy, viral infection, autoimmune disease, disease caused by regenerative dysfunction, autoimmune disease, cachexia, cardiovascular and cerebrovascular disease, neurodegenerative disease and aging, regulating autophagy, treating aging disease, etc., and has important medical value and research and application prospects.

The present invention discloses an application of a β3 adrenergic receptor (ADRB3) as a marker for detecting a plurality of diseases, and an application of anti-human ADRB3 monoclonal antibody in diagnosing a disease and preparing a drug for treating the disease. The present invention finds through research that the ADRB3 is a key receptor in nerve-endocrine-immunoregulatory network, and an ADRB3-mediated signaling pathway regulates proliferation and differentiation of neutrophils, lymphocytes and tumor cells. Under normal circumstances, the ADRB3 maintains the non-specific immunocompetence and specific immunocompetence of an organism, and eliminates pathogenic microorganisms and aged organism tissues to play a role in protecting the organism and anti-aging. Under pathological conditions, excessive activation of the signaling pathway will cause systemic chronic inflammation, and destroy immune homeostasis. Therefore, the ADRB3 can be used as a diagnostic marker and a therapeutic target for a plurality of diseases. Anti-human ADRB3 antibody can specifically bond with the ADRB3, regulate the activity of the ADRB3, has the functions of resisting cancer, inflammation, poisoning, shock, allergy, viral infection, autoimmune disease, disease caused by regenerative dysfunction, autoimmune disease, cachexia, cardiovascular and cerebrovascular disease, neurodegenerative disease and aging, regulating autophagy, treating aging disease, etc., and has important medical value and research and application prospects.

Novel methods for preventing, reducing the risk of development of, and for treating hypercoagulopathy in Cushing's syndrome patients with elevated risk of developing hypercoagulopathy are disclosed. The methods are further useful to prevent, to reduce the risk of developing, and to treat deep vein thrombosis (DVT), pulmonary embolism (PE), and venous thromboembolism (VTE); and to treat inflammatory states. The methods include: administering heteroaryl-ketone fused azadecalin glucocorticoid receptor modulator (HKGRM) to a Cushing's syndrome patient at risk of developing hypercoagulopathy, thereby treating hypercoagulopathy. Methods of preventing, reducing risk of developing, and of treating DVT, PR, or VTE in a Cushing's syndrome patient comprise administering a HKGRM to the patient. Methods of unmasking and subsequently reducing an inflammatory state comprise administering an effective amount of a HKGRM to a Cushing's syndrome patient, effective first to increase inflammatory symptoms and then to subsequently decrease said inflammatory symptoms in the patient.

Provided herein are methods for predicting whether a cancer patient will respond to treatment with bevacizumab based on determining a level of small extracellular vesicle (sEV)-associated VEGF in the patient. Also provided are methods of treating patients with either bevacizumab or a VEGFR tyrosine kinase inhibitor, a VEGFR neutralizing antibody, or a VEGF ligand trap based on the level of small extracellular vesicle (sEV)-associated VEGF in the patient.

Provided herein are methods for predicting whether a cancer patient will respond to treatment with bevacizumab based on determining a level of small extracellular vesicle (sEV)-associated VEGF in the patient. Also provided are methods of treating patients with either bevacizumab or a VEGFR tyrosine kinase inhibitor, a VEGFR neutralizing antibody, or a VEGF ligand trap based on the level of small extracellular vesicle (sEV)-associated VEGF in the patient.

A method for measuring a steroid in a urine sample comprising: an acid treatment step of mixing and reacting an urine sample with an acid solution such that a normality of acid becomes 0.6 to 4N to obtain an acid-treated solution; a neutralization treatment step of mixing and reacting the acid-treated solution and a neutralizing solution to obtain a neutralization-treated solution; and a measurement step of mixing the neutralization-treated solution and an antibody capable of specifically binding to a steroid to measure the steroid.

A heart failure marker that is simple, and preferably usable by non-invasive test. A method for measuring heart failure risk, comprising: (A) measuring an angiotensinogen amount value of urine collected from a subject.

A heart failure marker that is simple, and preferably usable by non-invasive test. A method for measuring heart failure risk, comprising: (A) measuring an angiotensinogen amount value of urine collected from a subject.

The present invention provides a synchronous detection method of medicaments influencing ARR in the detecting process of renin activity by liquid chromatography-tandem mass spectrometry. The method achieves the qualitative screening of medicaments influencing ARR values while detecting plasma renin activity by liquid chromatography-tandem mass spectrometry; moreover, the method can be used to assist to analyze and judge ARR as negative, positive, false negative or false positive. The detecting method achieves effective extraction of angiotensin I and 43 hypertension therapeutics synchronously through protein precipitation to samples, and enables to perform synchronous detection of a plurality of indices including angiotensin I and 43 hypertension therapeutics on the extracted sample by liquid chromatography-tandem mass spectrometry technology of high throughput, high specificity and high sensitivity. Moreover, the detection method utilizes the MRM mass spectrum parameters for preliminary screening of the medicaments, and rechecks the medicaments according to the retention time thereof. The ARR detection value is combined with the medicament screening result for co-analysis, which effectively distinguishes the false positive or false negative result of the detection while avoiding the patient's withdrawal of medicament for treatment, thereby improving the detection accuracy of the actual primary aldosteronism, and facilitating clinical promotion and application.