The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.

Methods and compositions are provided for treating weight related conditions and metabolic disorders by altering microbiota in a subject. One aspect provides methods and compositions to alter microbiota in a subject by administering to the subject a composition that includes a substantially purified microbiota from phyla such as Bacteroidetes, Proteobacteria, Firmicutes and Verrucomicrobia or orders such as Bacteroidales, Verrucomicrobiales, Clostridiales and Enterobacteriales or genera such as Alistipes, Clostridium, Escherichia, and Akkermansia. Another aspect includes a pharmaceutical composition for altering microbiota that includes a therapeutically effective amount of substantially purified microbiota and a pharmaceutically acceptable carrier. Yet another aspect includes methods for treating a disorder, such as obesity, in a subject in need of such treatment by changing relative abundance of microbiota in a gastrointestinal tract of the subject without or in addition to a surgical procedure.

Disclosed herein are substituted pyrazole-pyrimidine compounds of Formula I and variants thereof for the treatment, for example, of diseases associated with P2X purinergic receptors: ##STR00001##
In one embodiment, the P2X3 and/or P2X2/3 antagonists disclosed herein are potentially useful, for example, for the treatment of visceral organ, cardiovascular and pain-related diseases, conditions and disorders.

Disclosed herein are substituted pyrazole-pyrimidine compounds of Formula I and variants thereof for the treatment, for example, of diseases associated with P2X purinergic receptors: ##STR00001##
In one embodiment, the P2X3 and/or P2X2/3 antagonists disclosed herein are potentially useful, for example, for the treatment of visceral organ, cardiovascular and pain-related diseases, conditions and disorders.

The invention relates to differentiation methods for progenitor cells, e.g. mammalian epithelial stem cells, differentiation media for use in said methods, organoids and cells obtainable by said methods and uses, including therapeutic uses, thereof.

The present invention provides a method for preparing a pyrrolopyrimidine compound and application thereof. Specifically, the present invention provides a compound represented by formula I or pharmaceutically-acceptable salts thereof, a pharmaceutical composition containing the compound or its salts, and a method for preparing the pharmaceutical composition and an application of the pharmaceutical composition as an immunosuppressive drug. ##STR00001##

The present invention provides compounds, compositions thereof, and methods of using the same.

The present disclosure provides antibodies and antigen-binding fragments capable of binding PAR2. In some embodiments, the anti-PAR2 antibodies or antigen-binding fragments thereof bind PAR2 in a pH-dependent manner. The disclosure further provides methods for making and using the antibodies and antigen-binding fragments.

The present disclosure provides antibodies and antigen-binding fragments capable of binding PAR2. In some embodiments, the anti-PAR2 antibodies or antigen-binding fragments thereof bind PAR2 in a pH-dependent manner. The disclosure further provides methods for making and using the antibodies and antigen-binding fragments.

The present invention provides a macrocyclic compound of formula (I) ##STR00001## compositions and kits comprising this compound and their use for preventing or treating pain, or inducing hypothermia or hypotension.