Abstract: Described are niclosamide analogue compounds, pharmaceutical compositions thereof, and method of using the corner pounds and compositions for treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway, such as cancer, fatty liver, antibiotic resistance, and viral infection. The disclosed compounds and compositions may also be used for modulating mitochondrial function and for treating certain non-cancer diseases and/or diorders, such as diabetes, fibrotic disease, primary sclerosing cholangitis.

Abstract: A monolithic heat exchanger body for inputting heat to a closed-cycle engine includes heating walls and heat sink, such as heat transfer regions. The heating walls are configured and arranged in an array of spirals or spiral arcs relative to a longitudinal axis of an inlet plenum. Adjacent portions of the heating walls respectively define corresponding heating fluid pathways fluidly communicating with the inlet plenum. At least a portion of the heat sink is disposed about at least a portion of the monolithic heat exchanger body. The heat sink includes working-fluid bodies including working-fluid pathways that have a heat transfer relationship with the heating fluid pathways. Respective ones of the heat transfer regions have a heat transfer relationship with a corresponding semiannular portion of the heating fluid pathways. Respective ones of the heat transfer regions include working-fluid pathways fluidly communicating between a heat input region and a heat extraction region.

Abstract: A constant density heat exchanger and method of operating are provided. The constant density heat exchanger includes a housing extending between a first end and a second end and defining a chamber having an inlet and an outlet. A first plate is positioned at the first end of the housing and rotatable about an axis of rotation such that the first plate selectively allows a working fluid to flow into the inlet of the chamber. A second plate is positioned at the second end of the housing and rotatable about the axis of rotation such that the second plate selectively allows the working fluid to flow out of the outlet of the chamber. The first plate and the second plate are rotatable about the axis of rotation so as to hold a volume of the working fluid at constant density as a heat source imparts thermal energy thereto.

Abstract: The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of, or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject.

Abstract: The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of, or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject.

Abstract: Described are niclosamide analogue compounds, pharmaceutical compositions thereof, and method of using the corner pounds and compositions for treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway, such as cancer, fatty liver, antibiotic resistance, and viral infection. The disclosed compounds and compositions may also be used for modulating mitochondrial function and for treating certain non-cancer diseases and/or diorders, such as diabetes, fibrotic disease, primary sclerosing cholangitis.

Abstract: Described are methods of treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway. The methods include identifying subjects in need of therapy, administering inhibitors of the Wnt/Frizzled signaling pathway, pharmaceutical compositions including the inhibitors, and methods of using the compounds and compositions for treating cancer, bacterial and viral infection, lupus, type II diabetes, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) in a subject.

Abstract: Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

Abstract: Described are methods of treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway. The methods include identifying subjects in need of therapy, administering inhibitors of the Wnt/Frizzled signaling pathway, pharmaceutical compositions including the inhibitors, and methods of using the compounds and compositions for treating cancer, bacterial and viral infection, lupus, type II diabetes, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) in a subject.

Abstract: The present disclosure relates to methods of preventing or treating epilepsy comprising administering a receptor tyrosine kinase B (TrkB) inhibitor. In particular, the present disclosure relates to methods of treating a subject susceptible to the development of epilepsy, methods of inducing remission of epilepsy in a subject, and methods of transforming medically refractory epilepsy in a subject to medically responsive epilepsy comprising administering a therapeutically effective amount of a TrkB inhibitor or a phospholipase C?1 (PLC?1) inhibitor.

Abstract: Disclosed herein are conjugates of a therapeutic compound and polypeptides, such as a conjugate of niclosamide and an elastin-like polypeptide. These conjugates may form nanoparticles through self-assembly, which improve the solubility, bioavailability, and pharmacokinetic profiles of the therapeutic compound. Also disclosed are methods for treating cancer, parasite infection, bacterial infection, viral infection, metabolic diseases, Type II diabetes, NASH, NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, and systemic sclerosis.

Abstract: Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

Abstract: Described are methods of treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway. The methods include identifying subjects in need of therapy, administering inhibitors of the Wnt/Frizzled signaling pathway, pharmaceutical compositions including the inhibitors, and methods of using the compounds and compositions for treating cancer, bacterial Sand viral infection, lupus, type II diabetes, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) in a subject.

Abstract: Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

Abstract: The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject.

Abstract: Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

Abstract: Compounds of general Formulas (I), (IA), (IB) are described, along with compositions containing the same and methods of use thereof, inhibiting the hedgehog pathway in a cell or inhibiting unwanted proliferation of a cell.

Abstract: Compounds of general Formulas (I), (IA), (IB) are described, along with compositions containing the same and methods of use thereof, inhibiting the hedgehog pathway in a cell or inhibiting unwanted proliferation of a cell.

Abstract: The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of, or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject.

Abstract: Methods of treating Wnt/Frizzled-related diseases, comprising administering niclosamide compounds are provided. Methods of predicting whether a disease will respond to treatment with a niclosamide compound are also provided.