Abstract: The present invention provides compositions and methods for regulated gene expression. In certain aspects, the invention relates to an inducible synthetic promoter that can be used for regulated gene expression or to generate mutations in one or more bacterial cells of the gut microbiota.

Abstract: Provided herein are methods of determining tumoral sensitivity to hormonal (endocrine) therapy based upon an index of estrogen receptor (ER)- and progesterone receptor (PR)-related genes, referred to as the sensitivity to endocrine therapy index (SETER/PR index), and may have additional consideration for the proportion of ER gene (ESR1) RNA transcripts that contain a mutation relative to the value of the SETER/PR index. Further provided are methods of treating breast cancer patients determined to be sensitive to an endocrine therapy by the SETER/PR index.

Abstract: Disclosed herein are compositions and methods for detecting RNA binding sites and RNA interacting partners involving the use of a modified capture oligonucleotide having a dual toehold design.

Abstract: In one aspect, the invention comprises compounds that bind to the synaptic vesicle protein SV2A and that can be useful as radiotracers for positron emission tomography. In another aspect, the invention comprises methods of imaging the brain, measuring synaptic density or diagnosing neurological diseases such as Alzheimer's disease, psychiatric disorders such as depression, and metabolic disorders such as diabetes comprising detecting the compounds of the invention by positron emission tomography (PET).

Abstract: The invention provides a method of treatment comprising reducing therapy-induced adverse effects (TIAE), including chemotherapy-induced adverse effects (CIAE), such as chemotherapy-induced peripheral neuropathy (CIPN) and/or chemotherapy-induced cardiovascular adverse effects (CICAE) in a subject being treated with a CIAE-inducing anti-cancer active ingredient by co-administering to the subject a pharmaceutically effective amount of a NCS-1-protective composition. Related pharmaceutical compositions, diagnostics and screening techniques are also provided.

Abstract: Particles with a spatial and/or temporal release profile for delivery of different agents at different times to the same cells of a subject have been developed. The particles include a core polymeric particle containing a polymer and a first agent, a tethering moiety, covalent linker or covalent linkage attached to the core particle, and a tethered particle attached to the particle via the tethering moiety, covalent linker or covalent linkage and containing a second agent, where the agents are released at different times within or to the same cells. The first and second agents may be a therapeutic or prophylactic agent, such as an antigen, an immunomodulator, an anti-neoplastic agent, a hormone, an inhibitor, etc. The particles may form compositions for treating diseases with a spatial and/or temporal treatment regimen.

Abstract: The invention relates to methods of evaluating the quality of a batch of an herbal composition, the method comprising subjecting a test batch of the herbal composition to one or more biological analysis methods and comparing the results derived from the test batch to the results of a known batch of herbal composition which has a known in vivo effect.

Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Abstract: The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R4, G, Q, and ring A are defined herein. Aldehyde dehydrogenase inhibitors of Formula I are useful for treating a variety of conditions including cancer and inflammation. The disclosure includes methods for using compounds and salts of Formula I to treat colon cancer, pancreatic cancer, nasopharyngeal carcinoma, thyroid cancer, prostate cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, hepatocellular carcinoma, leukemia, brain tumors breast cancer, atherosclerosis, ischaemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, and interstitial cystitis.

Abstract: The present invention provides compounds and methods for treating, ameliorating, and/or preventing a MKP-5 modulated disease. In certain embodiments, the MKP-5 modulated disease is a fibrotic disease.

Abstract: Systems and methods for formal verification of programs. The systems and methods provide a new game-theoretical, strategy-based compositional semantic model for concurrency, a set of formal linking theorems for composing multithreaded and multicore concurrent layers, and a compiler that supports certified thread-safe compilation and linking. Verification of an overlay interface can include determining an intermediate strategy for a primitive operation running on an underlay interface and refining that intermediate strategy to a strategy running on the overlay interface by applying a vertical and a horizontal composition rule. The refined strategy can then be composed with compatible strategies running on the overlay interface according to a parallel composition rule. Strategies may be compatible when rely conditions imposed by each strategy satisfy guarantees provided by the other strategies. The system and method of formal verification can be applied to formal verification of smart contracts.

Abstract: The present invention relates to the discovery that inhibition of Dickkopf2 (DKK2) increases CD8+ cytotoxic T lymphocyte (CTL) activity, attenuates tumor angiogenesis, and hence suppresses tumor formation. Thus, in various embodiments described herein, the methods of the invention relate to methods of treating cancer by administering to a patient an effective amount of DKK2 gene depleting agent, methods for providing anti-tumor immunity and anti-tumor angiogenesis in a subject, methods of stimulating a T cell mediated immune response to a cell population or a tissue and suppressing tumor angiogenesis in a subject. Additionally, the current invention includes methods of diagnosing a cancer or a predisposition of developing a cancer or a metastasis and methods for determining the use of immunotherapy treatment or cancer vaccine for treating cancer. Furthermore, the invention encompasses a pharmaceutical composition for treating cancer as well as a kit for carrying out the aforementioned methods.

Abstract: The present invention provides methods and compositions for treating and preventing lung injuries due to or associated with coronavirus infections that cause Severe Acute Respiratory Syndrome, including COVID-19. More specifically the present invention provides methods for treating or preventing the lung injuries associated with SARS-CoV-2 infections, such as acute lung injury (ALI), lung fibrosis, and acute respiratory distress syndrome (ARDS). The methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a protein kinase inhibitor compound having MAP3K2/MAP3K3 inhibition activity, such as pazopanib or nintedanib, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, to a patient in need thereof. The present invention also provides devices for administering the compositions.

Abstract: Provided herein, in some embodiments, are compositions and methods for producing a molecular expression map of a biological sample using Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq).

Abstract: The present provides a Positional Isotopomer NMR Tracer Analysis (PINTA) method that can be used to noninvasively assess rates of hepatic mitochondrial oxidation (VCS) and/or pyruvate carboxylase (VPC) flux in a subject. In certain embodiments, the methods utilize a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3-13C]lactate and glucose tracer. The method of the invention provides investigators with a tool to non-invasively examine the role of altered hepatic mitochondrial metabolism and study the effects of therapeutic interventions for the treatment of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and type 2 diabetes (T2D).

Abstract: Catalysts for selective production of hydrogen peroxide and methods of making and using thereof have been developed. The catalysts include an alloyed or doped metal oxide which permits tuning of the catalytic properties of the catalysts for selection of a desired pathway to a product, such as hydrogen peroxide. The catalysts may be incorporated into electrochemical or photochemical devices.

Abstract: The methods and assays described herein relate to the diagnosis, prognosis, and treatment of subjects with emphysema, COPD, and/or cigarette-induced lung damage. In some embodiments, the methods and assays relate to subjects with a decreased level of NLRX1 expression. In some embodiments, the methods and assays relate to the administration of an agonist of NLRX1 and/or an inhibitor of MAVS.

Abstract: Supramolecular particle compositions based on medicinal natural products (MNPs), their synthetic analogs and derivatives, and methods to prepare and use them are provided. Five classes of MNPs and their derivatives including diterpene resin acid, phytosterol, lupane-type pentacyclic triterpene, oleanane-type pentacyclic triterpene, and lanostane-type triterpene form functional nano- or micro-structures that are stable to strong acidic environment and effectively penetrate the gastrointestinal tract. Therapeutic, prophylactic, or diagnostic agents that generally have poor intestinal permeability are converted to bioavailable forms when delivered with these supramolecular particles. Among many others, small compound chemotherapeutic agents and peptide therapeutics encapsulated therein have a much greater plasma concentration following oral administration, and effectively controls and treat symptoms associated with tumors or diabetes.

Abstract: The present invention includes DNP derivatives that are useful for preventing or treating a metabolic disease or disorder in a subject in need thereof. In certain embodiments, the subject is further administered at least one additional therapeutic agent.

Abstract: In one aspect, the invention comprises compounds that bind and inhibit macrophage migration inhibitory factor. In another aspect, the invention provides methods of treating inflammatory disease, neurological disorders and cancer using the compounds of the invention.