Abstract: The present invention relates to an antiviral application of nucleoside analogs. Specifically, the present invention relates to uses of nucleoside analogs and a pharmaceutical composition thereof as: (a) inhibitors for inhibiting the replication of coronaviruses, influenza viruses, respiratory syncytial viruses, flaviviridae viruses, filoviridae viruses and/or porcine epidemic diarrhea virus (PEDV); and/or (b) medicines for treating and/or preventing and mitigating diseases caused by coronavirus, influenza virus, respiratory syncytial virus, flaviviridae virus, filoviridae virus and/or porcine epidemic diarrhea virus (PEDV) infections. The nucleoside analogs according to the invention may treat and/or prevent and mitigate respiratory infection, pneumonia (COVID-19) and other related diseases caused by 2019 novel coronavirus infection.

Abstract: An anterograde monosynaptic transneuronal viral tracer system for mapping the direct postsynaptic targets of neurons in a given brain nucleus comprises a tracer H129-derived recombinant HSV-1 virion; and a helper AAV2/9-derived recombinant AAV2/9 virion; wherein the tracer H129-derived recombinant HSV-1 virion comprises a recombinant HSV-1-H129 viral genome with an impaired gK gene, and a mutant gK protein that pseudotypes the tracer H129-derived recombinant HSV-1 virion; and wherein the helper AAV2/9-derived recombinant AAV2/9 virion comprises a recombinant AAV2/9 viral genome that contains an HSV-1 H129 wild-type gK encoding sequence.

Abstract: The present application discloses a nucleic acid composition for expressing recombinant EBIV-related genes and proteins and the use thereof. The nucleic acid composition includes a nucleic acid molecule having sequences shown in SEQ ID NO. 14, 15, 16, and 17. In the present application, a recombinant EBIV is also constructed with this nucleic acid composition. The virus not only has broad-spectrum infectivity to mammalian and mosquito cells, can be stably passaged, but also has green fluorescence, which can provide a research foundation for in vitro and in vivo virus tracing, virus detection, antiviral drugs, vaccine screening, with significant application prospects.

Abstract: A salt of nucleoside analog, and crystal form, pharmaceutical composition and use thereof. The salt of nucleoside analog has a structure shown in formula I, wherein X is hydrogen or deuterium; Y is an acid, n is 0.5 to 2, or n is 1. When X is hydrogen or deuterium, Y is hydrogen bromide, and n is 1, the salt of the nucleoside analog exists in the form of a crystal with crystal form I or crystal form A or exists in an amorphous form.

Abstract: A method for down-regulating CD2AP expression in a subject comprises administering a CD2AP down-regulation composition to the subject, wherein the CD2AP down regulation composition is workable by way of siRNA/shRNA, CRISPR/Cas9, Talen or ZFNs; thereby the CD2AP expression in liver tissues of the subject is down-regulated.

Abstract: A recombinant Herpes Simplex Virus type 1 (HSV-1) strain H129-derived anterograde multi-synaptic transneuronal viral tracer for multi-synaptic neural circuit mapping comprises two or more fluorescence expression cassettes being integrated into the H129 genome at different locations; wherein each fluorescence expression cassette contains at least two copies of fluorescent protein-encoding sequence that are arranged in tandem, and at least one linker-encoding sequence, where at least one linker-encoding sequence is disposed between two fluorescent protein-encoding sequences, allowing transcription of fluorescent protein-encoding sequences and linker-encoding sequence as a single transcript; and wherein the linker-encoding sequence encodes a linker peptide containing at least two adjacent amino acids that are highly inefficient in forming a peptide bond between them; thereby, when the single transcript is translated, at least two fluorescent proteins are stoichiometrically generated due to the impedence of pepti

Abstract: A method for down-regulating CD2AP expression in a subject comprises administering a CD2AP down-regulation composition to the subject, wherein the CD2AP down regulation composition is workable by way of siRNA/shRNA, CRISPR/Cas9, Talen or ZFNs; thereby the CD2AP expression in liver tissues of the subject is down-regulated.

Abstract: A recombinant Herpes Simplex Virus type 1 (HSV-1) strain H129-derived anterograde multi-synaptic transneuronal viral tracer for multi-synaptic neural circuit mapping comprises two or more fluorescence expression cassettes being integrated into the H129 genome at different locations; wherein each fluorescence expression cassette contains at least two copies of fluorescent protein-encoding sequence that are arranged in tandem, and at least one linker-encoding sequence, where at least one linker-encoding sequence is disposed between two fluorescent protein-encoding sequences, allowing transcription of fluorescent protein-encoding sequences and linker-encoding sequence as a single transcript; and wherein the linker-encoding sequence encodes a linker peptide containing at least two adjacent amino acids that are highly inefficient in forming a peptide bond between them; thereby, when the single transcript is translated, at least two fluorescent proteins are stoichiometrically generated due to the impedence of pepti

Abstract: The present invention provides a CD81 and OCLN double transgenic mouse and its construction method and use. The double transgenic mouse can be used to constitute acute and chronic HCV infection in a mouse model.

Abstract: The present invention provides a vaccine composition for dental caries caused by S. mutans infection, where the vaccine composition comprises an antigen derived from a surface protein PAc of S. mutans and an adjuvant derived from flagellin. The present invention further provides methods for preparing the vaccine composition. The present invention also provides methods for preventing or curing dental caries caused by S. mutans by administrating to a subject the vaccine composition.

Abstract: A new gene —MN— and proteins/polypeptides encoded therefrom are disclosed. Recombinant nucleic acid molecules for expressing MN proteins/polypeptides and recombinant proteins are provided. Expression of the MN gene is disclosed as being associated with tumorigenicity, and the invention concerns methods and compositions for detecting and/or quantitating MN antigen and/or MN-specific antibodies in vertebrate samples that are diagnostic/prognostic for neoplastic and pre-neoplastic disease. MN-specific antibodies are disclosed that can be used diagnostically/prognostically, therapeutically, for imaging, and/or for affinity purification of MN proteins/polypeptides. The invention still further concerns antisense nucleic acid sequences that can be used to inhibit MN gene expression.

Abstract: The present invention provides a vaccine composition for dental caries caused by S. mutans infection, where the vaccine composition comprises an antigen derived from a surface protein PAc of S. mutans and an adjuvant derived from flagellin. The present invention further provides methods for preparing the vaccine composition. The present invention also provides methods for preventing or curing dental caries caused by S. mutans by administrating to a subject the vaccine composition.

Abstract: Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Screening assays are provided for identifying compounds, preferably organic compounds, preferably aromatic and heterocylic sulfonamides, which inhibit the enzymatic activity of MN/CA IX and that are useful for treating patients with preneoplastic/neoplastic disease. Further, the CA IX-specific inhibitors when labeled or linked to an appropriate visualizing means can also be used diagnostically/prognostically for preneoplastic/neoplastic disease, and for imaging use, for example, to detect hypoxic precancerous cells, tumors and/or metastases, by selectively binding to activated CA IX, preferably CA IX activated under hypoxic conditions, and not to inactive CA IX. Such detection of hypoxic conditions can be helpful in determining effective treatment options, and in predicting treatment outcome and the prognosis of disease development.

Abstract: The present invention provides an optimized recombinant flagellin protein and preparation and use thereof. The protein is with a deletion in the hypervariable region, said hypervariable region is the region from 180 to 400 amino acid of the flagellin protein, and the proteins include FliC?190-278, FliC?220-320 or FliC?180-400. The method of preparing said protein, comprising introducing a deletion into the hypervariable region of the flagellin protein. First constructed the flagellin protein recombinant plasmid, and then used it as template to construct the flagellin deletion cloning, and expressed and purified. The present invention also provides the use of the recombinant flagellin protein as adjuvant. The recombinant flagellin protein in present invention decreases the potential risks it may have, and decreases its antigenicity and immunogenicity and the inflammatory response induced by it, through deleting its main areas of immunogenicity and antigen activity.

Abstract: Herein disclosed are methods that are predictive of resistance to endocrine therapy in an estrogen receptor-positive (ER-positive) breast cancer patient. An exemplary method comprises detecting the overexpression of MN/CA9 gene expression product(s) in a sample from an affected subject, wherein if MN/CA9 is overexpressed, then the subject is considered to have a greater probability of resistance to endocrine therapy, particularly tamoxifen, and a corresponding poorer prognosis if undergoing endocrine therapy, than if MN/CA9 is not overexpressed. MN/CA9 gene expression products useful in the predictive/prognostic methods include MN/CA IX, MN proteins/polypeptides, MN nucleic acids and soluble MN/CA IX antigen (s-CA IX). The methods are useful as an aid in the selection of treatment for a patient with an ER-positive breast tumor.

Abstract: Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Screening assays are provided for identifying compounds, preferably organic compounds, preferably aromatic and heterocylic sulfonamides, which inhibit the enzymatic activity of MN/CA IX and that are useful for treating patients with preneoplastic/neoplastic disease. Further, the CA IX-specific inhibitors when labeled can also be used diagnostically/prognostically for preneoplastic/neoplastic disease, and for imaging use, for example, to detect hypoxic precancerous cells, tumors and/or metastases, by selectively binding to activated CA IX, preferably CA IX activated under hypoxic conditions, and not to inactive CA IX. Such detection of hypoxic conditions can be helpful in determining effective treatment options, and in predicting treatment outcome and the prognosis of disease development.

Abstract: A new gene—MN—and proteins/polypeptides encoded therefrom are disclosed. Recombinant nucleic acid molecules for expressing MN proteins/polypeptides and recombinant proteins are provided. Expression of the MN gene is disclosed as being associated with tumorigenicity, and the invention concerns methods and compositions for detecting and/or quantitating MN antigen and/or MN-specific antibodies in vertebrate samples that are diagnostic/prognostic for neoplastic and pre-neoplastic disease. MN-specific antibodies are disclosed that can be used diagnostically/prognostically, therapeutically, for imaging, and/or for affinity purification of MN proteins/polypeptides. The invention still further concerns antisense nucleic acid sequences that can be used to inhibit MN gene expression.

Abstract: Herein disclosed are methods that are prognostic for neoplastic/preneoplastic disease in a subject vertebrate, wherein said disease is associated with a tissue that normally expresses MN, but which MN expression is lost or diminished upon carcinogenesis. Exemplary of the types of preneoplastic/neoplastic diseases subject to the prognostic methods of this invention are those of gastric mucosa, gallbladder, biliary ducts, and ductal cells of duodenal glands. An exemplary prognostic method comprises comparing the level of MN gene expression product in a tissue sample from the affected subject, with the average MN gene expression product level found in analogous preneoplastic/neoplastic tissue samples; an above average MN gene expression product level indicates poorer prognosis for the subject. MN gene expression products useful in the prognostic methods include MN protein, MN polypeptide, and/or MN nucleic acids.

Abstract: Identified herein is the location of the MN protein binding site, and MN proteins/polypeptides that compete for attachment to vertebrate cells with immobilized MN protein. Such MN proteins/polypeptides prevent cell-cell adhesion and the formation of intercellular contacts. The MN protein binding site is a therapeutic target that can be blocked by organic or inorganic molecules, preferably organic molecules, more preferably proteins/polypeptides that specifically bind to that site. Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Vectors are provided that encode the variable domains of MN-specific antibodies and a flexible linker polypeptide separating those domains. Further vectors are disclosed that encode a cytotoxic protein/polypeptide operatively linked to the MN gene promoter or a MN gene promoter fragment comprising the HIF-1 consensus binding sequence, and which vectors preferably further encode a cytokine.

Abstract: Identified herein is the location of the MN protein binding site, and MN proteins/polypeptides that compete for attachment to vertebrate cells with immobilized MN protein. Such MN proteins/polypeptides prevent cell-cell adhesion and the formation of intercellular contacts. The MN protein binding site is a therapeutic target that can be blocked by organic or inorganic molecules, preferably organic molecules, more preferably proteins/polypeptides that specifically bind to that site. Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Vectors are provided that encode the variable domains of MN-specific antibodies and a flexible linker polypeptide separating those domains. Further vectors are disclosed that encode a cytotoxic protein/polypeptide operatively linked to the MN gene promoter, and which vectors preferably further encode a cytokine.