Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

A nitrogen-containing derivative of substituted phenol hydroxyl acid ester is represented by formula (I). A salt of the compound of formula (I) has good water solubility, and in vivo, can rapidly and completely release substituted phenols having a pharmacological effect, which can improve the water solubility of substituted phenols, rapidly exert the pharmacological effects of substituted phenols in vivo, and has good safety. The method for preparing the above-mentioned compound is provided. This compound can also be used in the preparation of drugs that produce anaesthesia and/or sedative and hypnotic effects on humans and animals.

##STR00001##

Disclosed are a 1,8-naphthalimide derivative, a preparation method therefor and a use thereof. The 1,8-naphthalimide derivative is easy to prepare, and is an enhanced Cu.sup.2+ fluorescent probe, which can detect Cu.sup.2+ by two wavelengths and be applied to almost-all-water systems. According to atitration experiments and blank experiments at 392 nm and 754 nm, the detection limit of the 1,8-naphthalimide derivative of the present invention for Cu.sup.2+ is 2.6368×10.sup.−7 mol/L and 2.0156×10.sup.−7 mol/L, respectively, indicating that same can perform quantitative detection for Cu.sup.2+ with a high selectivity and a high sensitivity by using two wavelengths. In addition, a pH colorimetric switch based on 1,8-naphthalimide can rapidly and reversibly respond to a pH by means of three ways: a maximum absorption wavelength, absorbance and color change. Same has a narrow switching pH range, a good selectivity and a high sensitivity, can be used in almost-all-water systems.

The invention provides compounds of Formula (I), or pharmaceutically acceptable salts thereof: ##STR00001##
The compounds, compositions, methods and kits of the invention are useful for the treatment of pain, itch, and neurogenic inflammation.

The invention provides compounds of Formula (I), or pharmaceutically acceptable salts thereof: ##STR00001## The compounds, compositions, methods and kits of the invention are useful for the treatment of pain, itch, and neurogenic inflammation.

The invention provides compounds of formula (I):

##STR00001##

wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of JAK kinases. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat gastrointestinal and other inflammatory diseases, and processes and intermediates useful for preparing such compounds.

The invention provides compounds of formula (I):

##STR00001##

wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of JAK kinases. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat gastrointestinal and other inflammatory diseases, and processes and intermediates useful for preparing such compounds.

The present disclosure provides nucleoside compounds and oligonucleotides including an unnatural 6-amino-2-pyridone heterocyclic base where the 6-amino and 2-positions are protected. The 2-position of the heterocyclic base can be protected with an acyl-oxy-methyl protecting group. In some embodiments, the protected heterocyclic base has the following structure where AcOM is an acetyl-oxy-methyl group and R is a ribose or deoxyribose sugar: ##STR00001## Methods for synthesizing an oligonucleotide are provided in which the subject compounds find use. The method can include protecting an unnatural (e.g., Z) nucleotide with an acetyl-oxy-methyl group; incorporating the protected unnatural nucleotide into a nucleotide sequence on a solid support; and removing the acetyl-oxy-methyl group from the unnatural nucleotide incorporated into the nucleotide sequence. The compounds and methods find use in the synthesis of long oligonucleotides including Z nucleotides.

The present disclosure provides nucleoside compounds and oligonucleotides including an unnatural 6-amino-2-pyridone heterocyclic base where the 6-amino and 2-positions are protected. The 2-position of the heterocyclic base can be protected with an acyl-oxy-methyl protecting group. In some embodiments, the protected heterocyclic base has the following structure where AcOM is an acetyl-oxy-methyl group and R is a ribose or deoxyribose sugar: ##STR00001## Methods for synthesizing an oligonucleotide are provided in which the subject compounds find use. The method can include protecting an unnatural (e.g., Z) nucleotide with an acetyl-oxy-methyl group; incorporating the protected unnatural nucleotide into a nucleotide sequence on a solid support; and removing the acetyl-oxy-methyl group from the unnatural nucleotide incorporated into the nucleotide sequence. The compounds and methods find use in the synthesis of long oligonucleotides including Z nucleotides.