Abstract: Genetically modified microorganisms that have the ability to convert carbon substrates into chemical products such as isobutanol are disclosed. For example, genetically modified methanotrophs that are capable of generating isobutanol at high titers from a methane source are disclosed. Methods of making these genetically modified microorganisms and methods of using them are also disclosed.

Abstract: Provided herein are engineered hepatitis B virus (HBV) molecular vaccine constructs. Vaccine constructs can also include ligand-inducible engineered gene switch systems for modulating expression of heterologous genes, such as a cytokines, in host cells.

Abstract: The biological production of beta-hydroxyisovalerate (?HIV) using at least one non-natural enzyme. The non-natural enzyme for the biologically-derived ?HIV provides more beta-hydroxyisovalerate synthase activity than the wild-type parent. The non-natural enzyme having one or more modifications of substrate-specificity positions. The non-natural enzyme can be expressed in a microorganism, such as a yeast or bacteria, wherein the microorganism comprises an active ?HIV metabolic pathway for the production of ?HIV. Alternatively, the non-natural enzyme can be a ?HIV synthase used to produce ?HIV in a cell-free environment. The biological derivation of ?HIV eliminates toxic by-products and impurities that result from the chemical production of ?HIV, such that ?HIV produced by a non-natural enzyme prior to any isolation or purification process has not been in substantial contact with any halogen-containing component.

Abstract: A polypeptide-coupled small molecule compound and its antiviral applications are provided. The polypeptide-coupled small molecule compound is obtained by linking a polypeptide with a sequence X?nLXGG and a small molecule compound capable of inhibiting activity of papain-like protease (PLpro) of coronavirus through a chemical bond. The polypeptide with the sequence X?nLXGG is a polypeptide with a sequence LXGG at its carboxyl terminal, X and X? are independently any amino acid, and n is an integer between 1-50. The structure of the small molecule compound capable of inhibiting the activity of PLpro contains an amino group or a hydroxyl group. The polypeptide-coupled small molecule compound can inhibit the PLpro of SARS-CoV-2 in a targeted manner, thereby inhibiting the polyprotein cleavage of coronavirus in the host, and achieving the purpose of inhibiting the replication of coronavirus in the host. It has the advantages of synergistic inhibition, low cytotoxicity and favorable solubility.

Abstract: Nanoparticles and formulations for preventing or reducing peri-/post-menopausal bone loss and/or obesity in a subject are disclosed. The nanoparticles contain a cage, such as a zeolitic imidazolate framework (“ZIF”), a surface modifying agent, a targeting ligand, and an active agent. The surface modifying agent is attached to the outer surface of the cage and the targeting ligand is exposed to the surrounding environment. The active agent is encapsulated in the cage. The targeting ligand binds to a reproductive hormone or a receptor of a reproductive hormone. The active agent can be a ribosome inactivating protein, an apoptosis inducer, a hormone, a receptor ligand, or a nucleic acid, or a combination thereof, that inactivate ribosomes of gonadotroph cells and/or prevent or reduce secretion of follicle-stimulating hormones in the subject. Uses for formulations incorporating the nanoparticles for preventing or reducing peri-/post-menopausal bone loss and/or obesity in a subject are also disclosed.

Abstract: Antibodies and antigen binding fragments thereof are provided that immunospecifically bind to PD-1 and induce or promote an immune response that activates immune cell proliferation or activity. Contrary to the existing paradigm that PD-1 exclusively promotes a suppressive immune response, the disclosed antibodies and antigen binding fragments thereof, immunospecifically bind to PD-1 and cause an activating signal to be delivered to the immune cell that activates the immune cell rather than suppressing the immune cell. In one embodiment, the disclosed antibodies and antigen binding fragments thereof specifically bind to PD-1 expressed on immune cells. The binding of the disclosed antibodies and antigen binding fragments thereof to PD-1 on immune cells causes an activating signal to be transmitted into the immune cell, for example a signal that enhances or promotes cytokine production and/or activation of immune cell proliferation.

Abstract: The present invention provides a method of detecting one or more Klebsiella species within a sample from a subject, the method comprising: subjecting DNA and/or RNA from the sample to a PCR amplification reaction using primer pairs targeting species-specific canonical single nucleotide polymorphisms (canSNPs); and analyzing amplification products resulting from the PCR amplification reaction to detect the one or more Klebsiella species. The present invention also provides a kit for detection of one or more Klebsiella species, Klebsiella clonal groups, AMR genes, and/or virulence genes, the kit comprising primer pairs targeting species-specific canSNPs, K. pneumoniae genes M1 and M2, clonal group-specific canSNPs, AMR genes, and/or virulence genes.

Abstract: The present invention relates to a method for introducing mutations into at least one target nucleic acid molecule comprising (a) providing at least one sample comprising at least one target nucleic acid molecule; and (b) amplifying the at least one target nucleic acid molecule using a low bias DNA polymerase. The present further relates to a use of a low bias DNA polymerase in a method for introducing mutations into one or more nucleic acid molecule(s), a group of sample tags, a method for designing the group of sample tags, a computer readable medium, and a method for preferentially amplifying target nucleic acid molecules.

Abstract: The invention provides bispecific heterodimeric antibodies with modified heavy chain IgG constant regions that promote efficient assembly of antibody heavy chain heterodimer pairs, as well as arm specific pairing of heavy and light chains.

Abstract: The present invention is related to a method of treating or preventing cancer in a subject comprising administering to a subject having cancer or prone of getting cancer a first agent that depletes the subject's regulatory T cells (Tregs); followed by administering to the subject a second agent comprising a checkpoint inhibitor.

Abstract: Methods of preparing mammalian enteroids, and methods producing T. gondii oocysts in vitro and in vivo in heterologous systems, are provided.

Abstract: Disclosed are a recombinant acid-resistant yeast having lactic acid-producing ability and suppressed glycerol production and a method of preparing lactic acid using the same. More particularly, disclosed are a recombinant acid-resistant yeast into which a gene involved in lactic acid production is introduced and in which a gene involved in glycerol production is deleted or attenuated, and a method of preparing lactic acid using the same. When producing lactic acid using the recombinant acid-resistant yeast, the production of lactic acid is maintained while the production of glycerol is reduced, so crosslinking by glycerol can be suppressed in the oligomerization reaction for conversion to lactide, and thus the conversion yield of lactic acid to lactide can be increased.

Abstract: Some embodiments of the methods and compositions provided herein relate to chimeric antigen receptors (CARs) that specifically bind to human extracellular domains of the IL-13 alpha 2 (IL13Ra2) receptor, cells containing such CARs, and methods of cell-based immunotherapy targeting cancer cells, such as cells of solid tumors.

Abstract: The invention relates to a method of treatment comprising administering a long-acting mutant human fibroblast growth factor to a subject in need thereof. The said long-acting mutant human fibroblast growth factor is mPEG-CH2—N?H-mFGF21, wherein mFGF21 consists of SEQ ID NO: 1, and the said new use consists of a method of treating non-alcoholic steatohepatitis.

Abstract: Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer, such as PTK7+ malignancies.

Abstract: Disclosed is a method for improving affinity of an antibody for an antigen, comprising, in an unmodified antibody, improving affinity for an antigen as compared to the unmodified antibody, by changing 17th, 18th and 20th amino acid residues of a light chain defined by Kabat method to charged amino acid residues.

Abstract: SIRPalpha-4-1BBL variant fusion proteins are provided. Also provided are isolated polypeptides comprising a SIRPalpha variant. Also provided are polynucleotides and nucleic acid constructs encoding the SIRPalpha-41BBL fusion protein or the isolated polypeptide, host-cells expressing same and methods of use thereof.

Abstract: Provided herein are microorganisms and methods for fermentative production of ?-ketoadipate from gaseous substrates such as carbon dioxide (CO2), carbon monoxide (CO), and/or hydrogen (H2). Additionally, the processes provided herein are methods for producing polymers containing ?-ketoadipate, that can potentially enable a circular economy by diverting waste, e.g., plastic waste.

Abstract: This invention relates to metabolically engineered microorganism strains, such as bacterial strains, in which there is an increased utilization of malonyl-CoA for production of a fatty acid or fatty acid derived product, wherein the modified microorganism produces fatty acyl-CoA intermediates via a malonyl-CoA dependent but malonyl-ACP independent mechanism.

Abstract: Provided herein are antibodies, or antigen binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen binding portions thereof.

Abstract: Provided are an anti-human claudin 18.2 monoclonal antibody and application thereof. The antibody has three heavy chain CDRs and three light chain CDRs, one of the three heavy chain CDRs and three light chain CDRs is as follows: a heavy chain CDR1 is SEQ ID NO: 1, a heavy chain CDR2 is SEQ ID NO: 2, a heavy chain CDR3 is SEQ ID NO: 3, a light chain CDR1 is SEQ ID NO: 4, a light chain CDR2 is SEQ ID NO: 5, and a light chain CDR3 is SEQ ID NO: 6.

Abstract: The present invention relates to methods and systems for cell lysis in a microfluidic device. More specifically, embodiments of the present invention relate to methods and systems for rapid continuous flow pathogen cell lysis. In one embodiment, the microfluidic device comprises a microfluidic channel, a microporous structure within the channel, and an enzyme immobilized on the surface of the microporous structure configured to lyse pathogen cells in fluid flowing through the microfluidic channel.

Abstract: A computer-implemented method is provided for simulating sensor data acquisition. The method may include receiving simulated sensor data corresponding with a synthetic object in a simulated three-dimensional (3D) environment. The method may also include identifying an object type corresponding with the synthetic object based on a location of the synthetic object in the simulated 3D environment. The method may further include associating an intensity value with the simulated sensor data based on the object type for the synthetic object.

Abstract: The present inventors confirmed that when a brazzein expression recombinant vector for high expression of brazzein in Saccharomyces cerevisiae was prepared and a S. cerevisiae strain Y2805 was transformed with the recombinant vector, the expression level of brazzein was particularly high, thereby completing an optimal expression system for mass-producing brazzein. Further, when the brazzein expression system is cultured under the optimal culture conditions according to the present invention, the amount of brazzein produced is further increased, the purification process is simple, and costs are reduced. Therefore, it is expected that the brazzein expression system according to the present invention can be widely used for mass-producing and commercializing brazzein, which is a sweet protein.

Abstract: The present application discloses genetically modified yeast cells comprising an active 3-HP fermentation pathway, and the use of these cells to produce 3-HP.

Abstract: A method for inducing a covert misclassification performed on a non-transitory computer readable medium, the method includes identifying a target position. The method further includes creating a spectral perturbation tensor. The spectral perturbation tensor is configured to shift a projection of an initial spectrum towards the target position. Additionally, the method includes combining the spectral perturbation tensor to the initial spectrum. Further, the method includes classifying the combination of the spectral perturbation tensor and the initial spectrum with an established classifier, thereby designing the spectral perturbation tensor such that the combination is misclassified.

Abstract: The present invention relates to a composition comprising at least one carrier comprising a polysaccharide, at least one antioxidant and at least one amino acid selected from cysteine, lysine, alanine and arginine. It also relates to the use of such a composition for the protection of microorganisms during drying, storage and/or reconstitution, to a culture powder, to a process of making the culture powder and to products comprising the culture powder.

Abstract: The present disclosure provides methods of integrating therapeutic protein and antibody generation and/or selection, evolution and expression in a eukaryotic host for manufacturing in a single system. Therapeutic proteins, including antibodies, are generated, optimized and manufactured in the same eukaryotic host system. The disclosed system of Comprehensive Integrated Antibody Optimization (CIAO!™) allows for simultaneous evolution of protein performance and expression optimization.

Abstract: Compositions and methods are provided for treating fibrosis in a mammal by administering a therapeutic dose of a pharmaceutical composition.

Abstract: Binding proteins comprising a VL region paired with a VH region, and a CH1 region paired with a CL region, wherein the VL region and VH region comprise opposite charged mutations to facilitate pairing, and wherein the CH1 region and CL region comprise mutations to facilitate pairing, are provided. Binding proteins comprising one or more cysteine residues engineered into the VH/VL pair to form one or more disulfide bonds, are also provided. Multispecific binding proteins, nucleic acids encoding binding proteins and multispecific binding proteins, expression vectors, host cells, pharmaceutical composition and methods of treatment administering the binding proteins or multispecific binding proteins described herein are also provided.

Abstract: The invention provides methods for improving efficiency of fermentation by arginine supplementation, and genetically modified bacterium for use therefor. More particularly the invention provides methods for (i) increasing the production ATP intensive products with arginine supplementation, (ii) increasing utilization of arginine by a C1-fixing bacterium; and (iii) providing C1-fixing bacterium with optimized arginine de-aminase pathways.

Abstract: The invention relates to a method for separating a polynucleotide insert from a polynucleotide vector backbone. The backbone has a plurality of cleavage sites distributed such that the backbone is converted into fragments when the sites are cleaved. This allows straightforward separation of the insert from the backbone. The invention also relates to backbones for use in such a method, and to plasmids and kits comprising such backbones.

Abstract: Provided herein compositions and methods for producing isoprenoids, including squalene. In certain aspects and embodiments provided are genetically converted yeast and uses therefore. In some aspects and embodiments, the genetically converted yeast produce isoprenoids, preferably squalene. Also are provided methods of producing squalene using a genetically converted yeast or a non-genetically converted yeast. The invention also provides squalene produced by genetically converted yeast or non-genetically converted yeast.

Abstract: The present disclosure relates to compounds, compositions, and methods for the inducing neurodegenerative disease pathologies. In one aspect, disclosed herein is a nucleotide sequence encoding a chimeric polypeptide, comprising: a first nucleotide sequence encoding a light-induced oligomerization domain and a second nucleotide sequence encoding a neurodegenerative disease in target protein. Disclosed herein is a method of inducing a neurodegenerative disease pathology in a cell, comprising the steps: introducing into the cell an expression vector encoding a chimeric polypeptide, comprising: a first nucleotide sequence encoding a light-induced oligomerization domain and a second nucleotide sequence encoding a low complexity domain from a neurodegenerative disease target protein, wherein the first nucleotide sequence is operably linked to a promoter; expressing the chimeric polypeptide; and inducing oligomerization of the chimeric polypeptide by stimulation with blue light.

Abstract: The present disclosure provides engineered transaminase enzymes having improved properties as compared to a naturally occurring wild-type transaminase enzyme. Also provided are polynucleotides encoding the engineered transaminase enzymes, host cells capable of expressing the engineered transaminase enzymes, and methods of using the engineered transaminase enzymes to synthesize a variety of chiral compounds.

Abstract: The present invention relates to genetically modified yeasts that can use lactate as a carbon source to produce a fermentation product. In one aspect, the yeasts can consume glucose and lactate simultaneously to produce ethanol. In one aspect, the genetically modified yeast is transformed to include a monocarboxylic/monocarboxylate transporter. In one aspect, the yeast can include one or more heterologous genes encoding lactate dehydrogenase (cytochrome) (EC 1.1.2.3 and/or 1.1.2.4).

Abstract: The present invention relates to isolated polypeptides having D-psicose 3-epimerase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Abstract: Some aspects of this disclosure relate to strategies, systems, methods, compositions, and kits that are useful for production (e.g., evolution) of cytidine deaminase protein variants that are characterized by increased soluble expression and/or stability relative to the wild-type cytidine deaminase protein from which they are evolved. In some embodiments, evolved cytidine deaminase variants described by the disclosure are useful for incorporation into targeted nucleic acid editing proteins, for example in fusion proteins with a Cas9 domain or variant thereof.

Abstract: The invention relates to recombinant Kluyveromyces lactis (K. lactis) yeasts which are capable of the highly efficient expression of one or more foreign proteins and are suitable for use as a vaccine for generating a protective immune response against pathogens. The invention provides in particular K. lactis strains for the targeted cloning of foreign antigen-coding nucleic acids into the yeast genome of the K. lactis strain, which is characterized in that the K. lactis strain has integrated expression cassettes for foreign antigens as an alternative or in addition to the KILAC4 locus on the KIURA3-20 locus (KLLA0E22771g) and/or on the KIMET5-1 locus (KLLA0B03938g). The invention further relates to integrative expression vectors and to methods for producing the K. lactis strains of the invention as well as to the use thereof as vaccines.

Abstract: Disclosed is a method for producing a modified antibody, comprising: in a heavy chain of the antibody, changing at least one amino acid residue selected from the group consisting of 8th to 11th amino acid residues based on Kabat method to a cysteine residue, and changing at least one amino acid residue selected from the group consisting of 109th and 110th amino acid residues based on IMGT method to a cysteine residue; and recovering the modified antibody.

Abstract: This invention relates to methods of expanding T regulatory cells through OX40L and Jagged-1 induced signaling. The methods can be used for treating autoimmune diseases.

Abstract: Disclosed is an expression cassette comprising, in a 5? to 3? direction of a sense strand, a promoter, and a first nucleic acid, a terminator and a second nucleic acid operably linked to the promoter, wherein the first nucleic acid and the second nucleic acid each contain at least one gene.

Abstract: The present disclosure provides methods and compositions for high fidelity in vitro transcription reactions.

Abstract: Provided herein are anti-Ly6G6D (lymphocyte antigen 6 complex, locus G61) antibodies and methods of using the same.

Abstract: The invention provides compositions and methods of treating cancer in a patient with a combination therapy comprising administering to the patient a fusion protein of SEQ ID NO: 1, in combination with an angiogenesis inhibitor (e.g., an anti-VEGF antibody or lenvatinib).

Abstract: The present invention provides an antimicrobial peptide ID13 (with a sequence set forth in SEQ ID NO. 1), a preparation method and use thereof. The antimicrobial peptide ID3 is successfully expressed in Pichia pastoris using genetic engineering technology. The antimicrobial peptide ID13 of the present invention has an excellent bactericidal activity against Gram-positive bacteria such as Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus suis, and has a low hemolytic activity against mouse red blood cells and a low murine macrophage cytotoxicity.

Abstract: A novel luciferase with a small molecular weight is provided. A polypeptide with luciferase activity comprising an amino acid sequence (A) or (B) is provided: (A) an amino acid sequence as set forth in SEQ ID NO: 1 with deletion of amino acid residues at positions 1 to 69 and 204 to 221; or (B) an amino acid sequence as set forth in SEQ ID NO: 1 with deletion of amino acid residues at positions 1 to 69 and deletion or substitution of at least one of amino acid residues 146 to 156.

Abstract: Cell culture media are provided herein as are methods of using the media for cell culture and protein production from cells.

Abstract: The present invention relates to an animal feed or an animal feed additive comprising Bacillus strains which improve the health and performance of production animals, and the use of such.

Abstract: The present application provides engineered polypeptides having imine reductase activity, polynucleotides encoding the engineered imine reductases, host cells capable of expressing the engineered imine reductases, and methods of using these engineered polypeptides with a range of ketone and amine substrate compounds to prepare secondary and tertiary amine product compounds.