Abstract: This disclosure provides compounds of Formula (I), Formula (II), and pharmaceutically acceptable salts thereof, that inhibit phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3K?). These chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) PI3K? activation contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing the same as well as methods of using and making the same.

Abstract: Forms of (S)-2-hydroxy-6-((4-(2-(2-hydroxyethyl)nicotinoyl)morpholin-3-yl)methoxy)benzaldehyde (Compound I), or salts or solvates thereof, were prepared and characterized in the solid state. Also provided are processes of manufacture and methods of using the forms of Compound I.

Abstract: The present invention relates to compounds of Formula (I): and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula (I), and methods of using the compounds of Formula (I) for treatment or prophylaxis of lysosomal storage diseases, neurodegenerative disease, cystic disease, cancer, or a diseases or disorders associated with elevated levels of glucosylceramide (GlcCer), glucosylsphingosine (GlcSph) and/or other glucosylceramide-based glycosphingolipids (GSLs).

Abstract: The present invention provides an industrially desirable production method for a sulfone derivative that is useful as a herbicide, and an intermediate thereof.

Abstract: Provided herein are macrocycle-based compounds or diastereomers, solvate, or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions and medicaments that include the compounds described herein as well as methods of treating fibrosis, inflammatory disease, and cancer.

Abstract: The disclosure provides a compound of formula I: or a salt thereof, wherein R1, R2, R4, L1, L2, and A have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful as TRPV4 antagonists.

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Abstract: Provided are thiazole derivative compounds that can reduce CD4+ IFN?+ T cells and inhibit or reduce inflammation. Also provided are methods of treating diseases characterized by gastrointestinal tract inflammation using the compounds.

Abstract: The present invention provides compounds of the structural Formula (I), and pharmaceutically acceptable salts thereof, wherein, are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.

Abstract: The present invention relates to novel fused imidazo pyrazole derivatives of formula (I), and formula (II), and methods for preparation thereof, in the presence of a chitosan-A203 nanocomposite film. The invention also relates to pharmaceutical compositions comprising compounds of the invention as active ingredients as well as the use of compounds of the invention for antimicrobial action.

Abstract: Provided herein are tuberculatin analogs that are useful as antivirals, such as anti-HIV, anti-coronaviral, anti-Ebola viral, and anti-influenza viral agents and methods of use thereof.

Abstract: The invention provides compounds that degrade the epidermal growth factor receptor (EGFR) including mutant forms via the ubiquitination of the EGFR protein and subsequent proteasomal degradation. The compounds are useful for the treatment of various cancers.

Abstract: The present invention relates to solid forms of 7-(5-chloro-2-(3-(5-cyano-6-(1-(3,3-difluorocyclobutyl)piperidin-4-yl)(methyl)amino)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)-N-(methylsulfonyl)thieno[3,2-b]pyridine-3-carboxamide, to pharmaceutical compositions comprising such solid forms, and to methods of using such solid forms and pharmaceutical compositions for the treatment of cancer.

Abstract: The present invention provides compounds of formula (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

Abstract: Embodiments of the present disclosure generally describe two-dimensional/three-dimensional conjugated salicylaldehydate metal organic framework (2D/3D-c-SA MOF) compositions, method for green synthesis of the two-dimensional/three-dimensional conjugated salicylaldehydate metal organic framework (2D/3D-c-SA MOF) compositions, applications of the said compositions in supercapacitors, lithium-ion batteries, electrocatalytic conversion reactions, photocatalytic reduction of CO2 and other uses.

Abstract: A method of producing a monomer composition including a polymerizable group-containing phosphoric acid compound is provided. The method includes a step of allowing a polymerizable group-containing alcohol compound, which is a compound not containing a urethane bond, to react with phosphorus pentoxide in the presence of a urethane compound, thereby obtaining a monomer composition including a polymerizable group-containing phosphoric acid compound.

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

Abstract: Provided herein are inhibitors of TNF-?, pharmaceutical compositions comprising the inhibitory compounds, and methods for using the TNF-? inhibitory compounds for the treatment of diseases or disorders.

Abstract: Provided are compounds of Formula Ir(LA)x(LC)y wherein: ligand LA has Formula I? ?and ligand LC has Formula II?

Abstract: The invention provides a new process for producing ruthenium complexes represented by the Formula 1. Invention provides also the use of ruthenium complexes represented by the Formula 1 as precatalysts and/or catalysts in olefin metathesis reactions.

Abstract: The present invention provides circularized RNA and methods of making, purifying, and using same.

Abstract: Provided herein are 19-nor C3, 3-disubstituted steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein R1, R2, R3, and R4 are as defined herein, and A is a heteroaryl ring system comprising 3 or 4 nitrogens as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

Abstract: A method for synthesizing peptide thioesters and a head-to-tail amide cyclic peptide thereof, which belongs to the technical field of chemical pharmaceuticals and fine chemical preparation. The method comprises the following steps: (1) using resin A as a carrier and using a solid-phase synthesis strategy to obtain a resin peptide; (2) cutting the resin to obtain a fully protected peptide; (3) performing an esterification reaction with p-chlorophenyl thiophenol in a TCFH/alkali condensation system to generate p-chlorophenyl thioester; (4) removing the protecting group to obtain a peptide thioester; and (5) further cyclizing to obtain a head-to-tail cyclic peptide. The preparation of the thioester peptide and the head-to-tail amide cyclic peptide provides a simple technical route with wide universality and a high yield, and has a wide range of applications in the technology of chemical pharmaceuticals and fine chemical preparation.

Abstract: A resin for an antibody purification and a chromatography column filled with the resin are provided, where small peptides are prepared for replacing protein A and binding to antibodies as well as protein A. The small peptides are easy and inexpensive to produce and resistant to proteases. Protease-resistant antibody binding peptides are synthesized on these resins, which is configured for the antibody purification directly.

Abstract: Disclosed is a polypeptide capable of prolonging the lifespan of Caenorhabditis elegans or pharmaceutically acceptable salts thereof. The polypeptide has an amino acid sequence TX1X2AA (X1X2: any amino acid, preferably AF/KA). Further, after one or more amino acids on the foregoing polypeptide sequence are deleted, substituted, or added, the resulting polypeptide or the pharmaceutically acceptable salts thereof still have the anti-aging activity. The polypeptide has the effect of prolonging the lifespan of Caenorhabditis elegans and anti-aging, and also has the function of enhancing the ability of movement behavior, improving the anti-stress ability, and alleviating the decline of movement ability in the aging process.

Abstract: The present invention relates to compositions comprising and methods for use of novel synthetic peptide antagonists. Antagonists of the invention inhibit the binding of acetylcholine to the muscle-type nicotinic acetylcholine receptor. They are useful in, e.g., cosmetics and pharmaceuticals that prevent or improve the appearance of undesirable skin features including wrinkles.

Abstract: Provided in the present disclosure are a KHL polypeptide, and the use thereof in the preparation of a TABP-EIC cell. In addition, also provided in the present disclosure are a KHL polypeptide conjugate, a tumor-antigen-binding polypeptide containing the KHL polypeptide, a DNA molecule, a carrier, a host cell and a pharmaceutical composition. The tumor-antigen-binding polypeptide is composed of the KHL polypeptide, a transmembrane domain and/or a signal transduction domain.

Abstract: Fusion Protein compositions comprising masked IFNs and methods of making masked IFNs are disclosed herein. Consequently, the masked IFNs can be fused to a Mab or binding fragment thereof and be administered to patients as a therapeutic modality and provide a method of treating cancer, immunological disorders and other disease.

Abstract: In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.

Abstract: The invention provides Epstein-Barr Virus antigen polynucleotides, polypeptides and vectors; as well as immunogenic compositions comprising the same. It includes the use of Epstein-Barr Virus antigen constructs to produce vaccines for treating and preventing Epstein-Barr Virus infections and Epstein-Barr Virus-associated diseases, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus.

Abstract: The present application provides a helper plasmid for preparing a recombinant adeno-associated virus (rAAV), including: 1) a coding sequence of an AAV Rep protein and a coding sequence of an AAV Cap protein; 2) at least one promoter sequence; and 3) at least one DA?sequence or AD? sequence, wherein the AD? sequence is a reverse complementary sequence of the DA? sequence. The present application also provides a method for increasing a production capacity of a rAAV using the helper plasmid. With an AD? sequence or a DA? sequence, the helper plasmid provided in the present application can significantly increase an AAV yield of a cell.

Abstract: The present invention is directed to methods of purifying viral proteins for use in vaccine compositions. The method includes a capture step and a polish step. The capture step includes passing a solution containing a protein over a hydrophobic interaction chromatography column and eluting a crude protein eluate from the column. The polish step includes passing the crude protein eluate over a ligand affinity chromatography column and recovering a first flow through intermediate, passing the first flow through intermediate over an anion exchange chromatography column and recovering a second flow through intermediate, and passing the second flow through intermediate over another ligand affinity chromatography column and recovering a purified protein eluate. The present invention also provides a purified protein having a hydrophobic membrane domain that is produced by a baculovirus expression system in cultured insect cells, wherein the purified protein has a purity of greater than 85%.

Abstract: Vaccination methods to control PCV2 infection with different PCV2 subtypes are disclosed. Specifically, a PCV2 subtype b (PCV2b) ORF2 proteins or immunogenic compositions comprising a PCV2b ORF2 protein are used in a method for the treatment or prevention of an infection with PCV2 of the same PCV2b and/or different subtype; the reduction, prevention or treatment of clinical signs caused by an infection with PCV2 of the same PCV2b or a different subtype; and/or the prevention or treatment of a disease caused by an infection with PCV2 of the same PCV2b and/or a different subtype. The present invention in particular relates to PCV2 subtype b (PCV2b) ORF2 proteins characterized in that they contain at least one mutation in the BC loop that such that the expressed protein is preferably expressed in a higher amount compared to a PCV2 ORF2 protein that does not contain such mutation.

Abstract: Barriers including crosslinked amphiphilic molecules, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids includes at least one layer comprising a plurality of amphiphilic molecules. Amphiphilic molecules of the plurality of amphiphilic molecules are crosslinked to one another.

Abstract: The disclosure relates to therapeutic proteins and pharmaceutical compositions comprising said proteins, which have utility in treating various human diseases. In particular aspects, the disclosed therapeutic proteins are useful for treating human gastrointestinal inflammatory diseases and gastrointestinal conditions associated with decreased epithelial cell barrier function or integrity. Further, the disclosed therapeutic proteins are useful for treating human inflammatory bowel disease, including inter alia, Crohn's disease and ulcerative colitis.

Abstract: Compositions having pesticidal activity and methods for their use are provided. Compositions include isolated and recombinant polypeptide sequences having pesticidal activity, recombinant and synthetic nucleic acid molecules encoding the pesticidal polypeptides, DNA constructs comprising the nucleic acid molecules, vectors comprising the nucleic acid molecules, host cells comprising the vectors, and antibodies to the pesticidal polypeptides. Nucleotide sequences encoding the polypeptides provided herein can be used in DNA constructs or expression cassettes for transformation and expression in organisms of interest. The compositions and methods provided herein are useful for the production of organisms with enhanced pest resistance or tolerance. Transgenic plants and seeds comprising a nucleotide sequence that encodes a pesticidal protein of the invention are also provided. Methods are provided for producing the polypeptides disclosed herein, and for using those polypeptides for controlling a pest.

Abstract: Immunogenic proteins from Pseudomonas aeruginosa as well as nucleic acids, vectors and transformed cells useful for expression of the proteins.

Abstract: The present invention relates to a modified MNEI protein comprising an amino acid sequence that has two or more amino acids deletions, insertions, replacements, or any combination thereof, from a reference MNEI protein, wherein the modified MNEI protein has at least one improved food-related property compared to the reference MNEI protein; and to uses thereof in the food industry.

Abstract: The present invention relates to a hexatoxin peptide variant comprising a. an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs: 27 to 29, wherein the amino acid sequence has at least one amino acid variant on position N27; b. an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs: 2, 6, 7, 30 or 32, wherein the amino acid sequence has at least one amino acid variant on position N28; c. an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs: 1, 3, 4, 5, 8 to 24 or 31, wherein the amino acid sequence has at least one amino acid variant on position N29; d. an amino acid sequence which is at least 90% identical to SEQ ID NO: 25, wherein the amino acid sequence has at least one amino acid variant on position N30; e. an amino acid sequence which is at least 90% identical to SEQ ID NOs: 26, wherein the amino acid sequence has at least one amino acid variant on position N31; or f.

Abstract: The present invention provides novel blockers of the potassium channel Kv1.3, polynucleotides encoding them, and methods of making and using them.

Abstract: The present disclosure relates to methods for production of (Z)-11-hexadecen-1-ol in a yeast cell. Also disclosed are methods for production of (Z)-11-hexadecenal in a yeast cell. Also disclosed are methods for production of (Z)-11-hexadecen-1-yl acetate in a yeast cell. The disclosure also provides for nucleic acid constructs and yeast cells useful for performing the present methods, as well as to pheromone compositions.

Abstract: The present invention is directed to a fusion protein comprising a scaffold protein and a series of two or more epitopes, where the distinct epitopes are recognized by distinct antibodies, and where the series of epitopes forms a detectable protein tag. The present invention further relates to a nucleic acid molecule encoding a nucleic acid sequence encoding the fusion protein, as well as vectors comprising the nucleic acid molecule. Methods of tracking a cell and kits using such vectors are also disclosed.

Abstract: The present disclosure relates to prodrugs or chimeric molecules which comprise a carrier moiety, a cytokine moiety selected from an IL-10 agonist polypeptide and a TGF-? agonist polypeptide, and a masking moiety that binds to said cytokine moiety and inhibits its biological activity. Further included in the present disclosure are methods of making and using the novel prodrugs or chimeric molecules.

Abstract: The present invention relates to a mammalian FGF21 responsive reporter cell line and method of using the same for detecting and optionally quantitating FGF21 activity in a test sample. The invention further relates to a method for detecting and optionally quantitating neutralizing antibodies against FGF21 present in a test sample using the reporter cell line of the present invention.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: This invention provides for a fusion protein between a single chain TNFR2 Selective Agonist protein (scTNFR2 Selective Agonist) and a dimerization domain, such as an IgGFc protein. The single chain TNFR2 Selective Agonist moiety provides a therapeutic activity by selectively activating the TNFR2 form of the TNF-? receptor, thus selectively stimulating Tregs and/or increasing myelin deposition.

Abstract: The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

Abstract: The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

Abstract: The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

Abstract: The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.