The present disclosure relates to a crystal form of a pyridopyrimidine derivative and a preparation method thereof, and specifically relates to the crystal form of the compound of formula (I) and a preparation method thereof. The new crystal form has good physical and chemical properties, thereby facilitating clinical treatments.

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The present invention discloses a preparation method for a disubstituted PEGylated interleukin 2, which comprises the steps of: (1) PEGylating IL-2 to obtain a crude product of a PEGylated interleukin; (2) performing gel chromatography filtration to remove free interleukin 2 from the crude product; (3) performing affinity chromatography on the product in the step (2) by means of an α receptor column, and collecting a flow-through peak component and an elution peak component; (4) performing ion exchange separation on the flow-through peak component and the elution peak component in the step (3); and (5) collecting components of the disubstituted PEGylated interleukin 2.

Provided herein are non-naturally occurring, broadly reactive antigens derived from influenza viruses or avian infectious bronchitis virus (IBV) that are immunogenic and capable of eliciting a broadly reactive immune response, e.g., a broadly reactive neutralizing antibody response, directed against influenza virus antigens or IBV antigens following introduction into a subject. Also provided are non-naturally, broadly reactive immunogens, vaccines, virus-like particles (VLPs) and compositions comprising the immunogens and vaccines. Methods of generating an immune response in a human or non-human subject by administering the immunogens, vaccines, VLPs, or compositions thereof are provided. In particular, the immunogens comprise broadly reactive hemagglutinin (HA) protein antigens of influenza virus strains, such as H1, H2, H3, H5, or H7, or of IBV. The immunogens also comprise broadly reactive viral neuraminidase (NA) protein antigens.

Provided herein are non-naturally occurring, broadly reactive antigens derived from influenza viruses or avian infectious bronchitis virus (IBV) that are immunogenic and capable of eliciting a broadly reactive immune response, e.g., a broadly reactive neutralizing antibody response, directed against influenza virus antigens or IBV antigens following introduction into a subject. Also provided are non-naturally, broadly reactive immunogens, vaccines, virus-like particles (VLPs) and compositions comprising the immunogens and vaccines. Methods of generating an immune response in a human or non-human subject by administering the immunogens, vaccines, VLPs, or compositions thereof are provided. In particular, the immunogens comprise broadly reactive hemagglutinin (HA) protein antigens of influenza virus strains, such as H1, H2, H3, H5, or H7, or of IBV. The immunogens also comprise broadly reactive viral neuraminidase (NA) protein antigens.

A natural immune agonist complex, consisting of an immune agonist and a targeted liposome, where the immune agonist is M(cGAMP)L.sub.n. The targeted liposome is formed by a nanobody targeting a tumor microenvironment, a cell membrane-targeted penetrating peptide, or a blood-brain barrier-targeted penetrating peptide with a liposome through chemical bonding. This application further provides a preparation and application of the natural immune agonist complex.

A pharmaceutical composition for treating an influenza virus infectious disease, containing an anti-influenza virus agent as an active ingredient is provided. The anti-influenza virus agent is administered to a patient determined to be positive for the influenza virus infectious disease based on an intraoral image captured using an intraoral imaging apparatus.

Compositions and methods comprising Pulmonary Surfactant (PS)-biomimetic nanoparticles are disclosed. Specifically, the disclosure is related to a composition comprising a nanoparticle with an average size of 200-400 nm, including a plurality of pulmonary surfactant biomimetic molecules, wherein the nanoparticle is negatively charged; and one or more cargo molecules that are enveloped by the nanoparticle, wherein the cargo molecule has a molecular weight up to 1200 Da.

Compositions and methods comprising Pulmonary Surfactant (PS)-biomimetic nanoparticles are disclosed. Specifically, the disclosure is related to a composition comprising a nanoparticle with an average size of 200-400 nm, including a plurality of pulmonary surfactant biomimetic molecules, wherein the nanoparticle is negatively charged; and one or more cargo molecules that are enveloped by the nanoparticle, wherein the cargo molecule has a molecular weight up to 1200 Da.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use ribonucleic acid vaccines comprising polynucleotide molecules encoding one or more influenza antigens, such as hemagglutinin antigens.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use ribonucleic acid vaccines comprising polynucleotide molecules encoding one or more influenza antigens, such as hemagglutinin antigens.