The present invention includes a method for detecting or predicting a disease or condition related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio) comprising: obtaining or having obtained a biological sample from a subject; and determining the LH/FSH ratio in the biological sample, wherein a decrease in the LH/FSH ratio when compared to an age-matched subject that does not have a disease or condition of LH/FSH is indicative of a current or future disease or condition of LH/FSH.

In some aspects, disclosed herein are methods and compositions for treatment of sclerosing cholangitis using fibroblasts or derivatives thereof. The disclosed compositions include fibroblasts, engineered fibroblasts, exosomes obtained from fibroblasts, and conditioned media derived from fibroblasts. Methods of the present disclosure include providing fibroblasts to a subject to treat sclerosing cholangitis in the subject. Fibroblasts of the disclosure include fibroblasts capable of reducing inflammation in a subject. In certain aspects, fibroblasts are cultured with activating agents prior to therapeutic administration.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of long-lived polynucleotides, primary transcripts and mmRNA molecules.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of long-lived polynucleotides, primary transcripts and mmRNA molecules.

A highly glycosylated human blood-clotting factor VIII (FVIII) fusion protein, and a manufacturing method and application of same. The fusion protein comprises, from the N-terminus to the C-terminus, a human (FVIII), a flexible peptide connector, at least one rigid unit of a human chorionic gonadotropin β-subunit carboxyl terminal peptide, and a half-life extending portion (preferentially selected from a human IgG Fc variant). The fusion protein has a similar level of biological activity as a recombinant (FVIII) and an extended in vivo half-life, thereby improving pharmacokinetics and drug efficacy.

A highly glycosylated human blood-clotting factor VIII (FVIII) fusion protein, and a manufacturing method and application of same. The fusion protein comprises, from the N-terminus to the C-terminus, a human (FVIII), a flexible peptide connector, at least one rigid unit of a human chorionic gonadotropin β-subunit carboxyl terminal peptide, and a half-life extending portion (preferentially selected from a human IgG Fc variant). The fusion protein has a similar level of biological activity as a recombinant (FVIII) and an extended in vivo half-life, thereby improving pharmacokinetics and drug efficacy.

A hyperglycosylated recombinant human coagulation factor IX (FIX) fusion protein, a preparation method therefor, and use thereof. The fusion protein sequentially comprises, from N- to C-terminus, a human FIX, a flexible peptide linker, at least one human chorionic gonadotropin β subunit carboxy-terminal peptide rigid unit, and a half-life extending moiety. The fusion protein has a biological activity similar to that of the recombinant FIX, an extended in vivo activity half-life, and reduced immunogenicity, so as to improve pharmacokinetics and pharmacodynamics.

A hyperglycosylated recombinant human coagulation factor IX (FIX) fusion protein, a preparation method therefor, and use thereof. The fusion protein sequentially comprises, from N- to C-terminus, a human FIX, a flexible peptide linker, at least one human chorionic gonadotropin β subunit carboxy-terminal peptide rigid unit, and a half-life extending moiety. The fusion protein has a biological activity similar to that of the recombinant FIX, an extended in vivo activity half-life, and reduced immunogenicity, so as to improve pharmacokinetics and pharmacodynamics.

Provided are recombinant Factor VIII proteins, e.g., human Factor VIII proteins with heterologous moieties inserted into flexible permissive loops located in the Factor VIII A domains, while retaining the procoagulant activity of Factor VIII.

Provided are recombinant Factor VIII proteins, e.g., human Factor VIII proteins with heterologous moieties inserted into flexible permissive loops located in the Factor VIII A domains, while retaining the procoagulant activity of Factor VIII.