Abstract: Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Abstract: Disclosed multifunctional compounds, conjugates, macromolecules, and polymers that target dysregulated proteins for degradation. Also disclosed are methods of preparation, compositions, kits, and methods of use relating to the degraders.

Abstract: A drilling fluid composition comprising a base fluid, and a viscosifier including an ultra-high molecular weight branched block copolymer having the following structure, where monomer A is an anionic monomer, monomer B is a hydrophilic monomer, monomer C is an anionic monomer, monomer D is a crosslinker-divinyl monomer, and —SSCZ ground being a terminal RAFT agent.

Abstract: The present disclosure relates generally to compounds comprising oligonucleotides complementary to a cystic fibrosis transmembrane conductance regulator (CFTR) RNA transcript. Certain such compounds are useful for hybridizing to a CFTR RNA transcript, including but not limited to a CFTR RNA transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the CFTR transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with Cystic Fibrosis.

Abstract: This invention relates to anti-CD70 antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are ?CD70 antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the ?CD70 antibodies of the invention are conjugated to one or more toxins. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: A laminate including a base member, and a hydrogel layer whose forming material is a hydrogel, the hydrogel layer being provided on a surface of the base member. An adhesive region and a non-adhesive region are formed at an interface between the base member and the hydrogel layer, the adhesive region being a region where the base member and the hydrogel layer adhere to each other, the non-adhesive region being a region where the base member and the hydrogel layer do not adhere to each other.

Abstract: The invention features a composition comprising a potent cytotoxic compound and a pH low insertion peptide, where, e.g., the cytotoxic compound cannot be used alone due to a lack of targeting. The pH low insertion peptide targets cytotoxic compounds to acidic diseased tissue, translocates cytotoxic compounds across plasma membranes into the cytosols of cells in acidic diseased tissues and induces cell death predominantly in the targeted acidic diseased tissue.

Abstract: Provided are methods and compositions for treating cancer in a subject in need thereof. One of the top gene products in glioblastoma multiforme (GBM) is KLRB1 (also known as CD161), a C-type lectin protein that binds to CLEC2D. Binding of CLEC2D to the KLRB1 receptor inhibits the cytotoxic function of NK cells as well as cytokine secretion. KLRB1 is only expressed by small subpopulations of human blood T cells, and consequently little is known about the function of this receptor in T cells. However, preliminary data demonstrate that KLRB1 expression is induced in T cells within the GBM microenvironment. In an exemplary embodiment, a method is provided comprising administering an agent capable of blocking the interaction of KLRB1 with its ligand. The agent may comprise an antibody or fragment thereof, which may bind KLRB1 or CLEC2D.

Abstract: A microfluidic chip for causing the delivery of a payload to a cell comprises a plurality of constrictions configured to allow a cell suspension to flow through one or more of the plurality of constrictions from a first fluid flow region to a second fluid flow region within the microfluidic chip, wherein a cross-sectional width of each of the plurality of constrictions is less than a diameter of cells in the cell suspension, such that membranes of the cells are perturbed when passing through the constrictions such that a payload is able to pass through the perturbed cell membranes, and wherein a quotient of a cross-sectional area over a cross-sectional perimeter of each of the plurality of constrictions is greater than greater than or equal to 0.5 ?m.

Abstract: The disclosure provides a method comprising (1) conducting a PCR using a nucleic acid sample obtained from the subject as the template, a forward primer having a nucleic acid sequence of a part of exon 1 of the BCR gene, and a reverse primer having a nucleic acid sequence complementary to a part of exons 2 to 11 of the ABL1 gene, in the presence of a modified nucleic acid having a nucleic acid sequence of a part of exons 2 to 14 of the BCR gene or a nucleic acid sequence complementary thereto; and (2) determining that the subject has the minor BCR-ABL1 gene when the nucleic acid amplification is occurred in the PCR.

Abstract: Novel pyrido[4,3-e] [1,2,3]triazolo[1,5-a]pyrimidine compounds, a method of synthesizing said compounds, a pharmaceutical composition comprising said compounds and a suitable carrier, and a method of using the compounds. The pyrido[4,3-e] [1,2,3]triazolo[1,5-a]pyrimidine compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Abstract: Provided herein are methods of in-vitro primary T cell growth that enrich T cells in a blood sample, stimulate the T cells with anti-CD2, anti-CD3, and/or anti-CD28 and that expand the T cells with a cytokine. Also provided are methods of treating a tumor in a patient using the expanded T cells.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Abstract: A method of preventing metastasis of a cancer in a patient in need thereof includes administering to the patient a therapeutically effective amount of ibudilast, or a pharmaceutical salt thereof.

Abstract: The invention provides methods of depleting CD5+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD5 antibody drug conjugates (ADCs) are administered as a conditioning regimen to a human patient receiving autologous or allogeneic CAR expressing immune cells such that the CAR expressing immune cells are accepted by the human patient. Compositions and methods of the invention can be used in combination with CAR therapy to treat a variety of pathologies, including autoimmune diseases and cancer.

Abstract: A method efficiently produces cytotoxic T lymphocytes having intrinsic properties of lymphocytes of the acquired immune system suitable for cellular immunotherapy. The method includes culturing CD4/CD8 double-positive T cells in a medium containing IL-7 and a T-cell receptor activator, to induce CD8?+?+ cytotoxic T lymphocytes.

Abstract: A composition of drug targets and the method of using thereof. The composition comprises a vector and a drug using FKBP10 and PCOLCE genes and/or the encoded proteins thereof as drug targets.

Abstract: A method for measuring interactions between labeled particles and ligands comprising the steps: a) providing a sample comprising labeled particles and ligands in a solution, wherein the labeled particles are dissolved or dispersed in the solution or are immobilized on a solid support; b) exciting fluorescently the labeled particles and detecting the fluorescence of the excited particles at a predetermined temperature; c) repeating steps (a) and (b) multiple times at different concentrations of the ligands in the solution; and d) determining the interaction between the labeled particles and the ligands based on the ligand concentration dependent change of the fluorescence of the labeled particles, wherein the labeled particles are labeled with one or more dyes.

Abstract: Provided is a composition for accelerating cell proliferation, including an erythropoietin-derived peptide as an active ingredient. Due to having a simpler structure than that of the existing natural human erythropoietin, the composition easily passes through the tissue-blood barrier, exhibits excellent cell protective activity, does not cause side effects of cell proliferation, and improves a hematopoietic function. Accordingly, the composition is used in the treatment or prevention of an anemic disorder.

Abstract: Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed, More particularly, an isolated peptide comprising the amino acid sequence LRRFSTAPFAFIDINDVINF, which exhibits anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumorigenic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models is disclosed. The isolate peptide also exhibits anti-lymphangiogenic and directly anti-tumorigenic properties.

Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

Abstract: The present invention relates to a chimeric antigen receptor (CAR) specific for an IL-23 receptor, and to a nucleic acid encoding the same. The present invention further relates to a T cell expressing said CAR, and to the use thereof for treating an autoimmune and/or inflammatory disease or disorder.

Abstract: A compound represented by formula (I) or a tautomer, an optical isomer, a nitrogen oxide, a solvate, a pharmaceutically acceptable salt or prodrug thereof are useful for treating or relieving an HIF-related and/or EPO-related disease or condition in patient. The preparation method for the compound, and use of a drug composition containing the compound and the compound or the drug composition in preparation of a drug are also provided.

Abstract: This disclosure relates to methods of treatment using compound (1) or analogs thereof, and pharmaceutically acceptable salts thereof. Also disclosed are compounds of formula (10): as defined in the specification, and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising the same. Methods of treatment, such as for cancer, are provided that comprise administering the compounds and their salts to a subject in need of such treatment.

Abstract: The present invention relates to compositions comprising induced T regulatory cells (iTregs), methods of making the compositions, and methods of using the compositions for enhancing bone remodeling in the treatment of Osteogenesis Imperfecta (OI).

Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

Abstract: Described herein are methods for treating or preventing a disease or disorder of the pulmonary system (e.g., cystic fibrosis), respiratory or digestive system in a subject, the methods comprising administering compounds or compositions comprising water soluble polyglucosamine and derivatized polyglucosamine.

Abstract: A method for producing uniform-size liposomes is provided. The liposomes are coated with a sorting agent to yield a plurality of density-modified liposomes of different sizes. These liposomes are then separated using a densitometric method. The sorting agent includes both a density-modifying moiety and a targeting moiety.

Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of PHD2 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against PHD2 gene expression.

Abstract: Methods of minimizing dysregulation of Staufen1-associated RNA metabolism can include introducing an amount of a Staufen1-regulating agent to a target cell sufficient to minimize the dysregulation. Therapeutic compositions for treating a neurodegenerative condition associated with Staufen1-induced dysregulation of RNA metabolism can include a therapeutically effective amount of a Staufen1-regulating agent and a pharmaceutically acceptable carrier.

Abstract: Described herein are methods and culture medium, useful for inducing polarization in multipotent stem cells. Additionally, described herein are multipotent cells produced by the methods and culture medium of this disclosure that are useful therapeutic agents. Also described herein are extracellular vesicles and factors secreted by multipotent cells that are produced by the methods and culture medium of this disclosure that are useful as therapeutic agents.

Abstract: The present invention relates to mitochondrial compositions and therapeutic methods of using same. The invention discloses compositions of partially purified functional mitochondria and methods of using the compositions to treat conditions which benefit from increased mitochondrial function by administering the compositions to a subject in need thereof.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: Retrotransposons, operating though human-specific neurological pathways, can contribute to environment, lifestyle, and/or age-related neurodegeneration by disrupting functional mitochondrial populations within neurons. The mitochondrial disruption can occur through a number of retrotransposon-induced mechanisms that can influence the efficient and accurate transcription and/or translation of mitochondrial genes encoded in the nuclear genome, operating primarily through epigenetic processes. Alu element-related conformational changes (both subtle and major) of the outer and inner mitochondrial membrane pores can restrict or prevent the normal translocation of proteins (i.e., TOMM and TIMM complexes), ultimately contributing to mitochondrial stress, mitophagy, inflammation, and neuron and glial cell death.

Abstract: A method of preventing or treating a subject suffering from a flavivirus infection by administering an effective amount of berbamine or its analogue to the subject, berbamine has a structure of Formula (I), wherein the flavivirus infection is caused by Japanese encephalitis virus, Zika virus or Dengue virus. A method of inhibiting the entry of a flavivirus, an enterovirus and/or a lentivirus into host cells includes contacting the host cells with an effective amount of berbamine of its analogue, berbamine has a structure of Formula (I), wherein the flavivirus is Japanese encephalitis virus, Zika virus or Dengue virus.

Abstract: The invention relates to an allele specific siRNA able to silence the expression of only one allele of a heterozygous DNM2 gene, for treating diseases caused by heterozygous mutation and/or overexpression of Dynamin 2.

Abstract: An antibody or fragment thereof, against presenilin, and more specifically against the luminal loop 1 of presenilin, for use in the treatment of cancer, by way of administrating a therapeutically effective quantity of the antibody or a fragment thereof, or a pharmaceutical composition comprising thereof, to a subject who suffers from cancer.

Abstract: Provided are T cell receptors (TCR) and TCR variable regions that can selectively bind the T-cell leukemia/lymphoma 1 (TCL1) oncoprotein. The TCR may be utilized in various therapies, such as autologous TCL1-TCR adoptive T cell therapy, to treat a cancer, such as a B-cell malignancy or a solid tumor expressing TCL1. Methods for expanding a population of T cells that target TCL1 are also provided.

Abstract: The disclosure provides compositions and methods of treating diseases and conditions associated with phospholipase D (PLD) toxin. In particular, the methods include administering to a subject in need a pharmaceutical composition comprising a dicarboxylic acid ester.

Abstract: Antisense oligonucleotides target the mutation in intron 26 of the CEP290 gene and reduce inclusion of the aberrant exon into the CEP290 mRNA. The oligonucleotides include no more than 3 consecutive guanosines, have no more than 60% guanosine nucleobases, include at most one CpG sequence, and/or do not have the potential to form a hairpin comprising 3 or more consecutive complementary base pairs.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.

Abstract: The present invention provides compositions and methods for stimulating an immune response using cationic lipids alone or in combination with antigens.

Abstract: The present disclosure relates to antisense oligomers and related compositions and methods for increasing the expression of functional human type VII collagen and methods for treating dystrophic epidermolysis bullosa and related disorders and relates to inducing exclusion of exon 80 in human type VII collagen mRNA.

Abstract: The present invention is related to compositions and methods for activating Lck, including in vivo, in vitro and ex vivo uses.

Abstract: The disclosure provides compositions and methods of inducing an analgesic effect. In particular, the methods include administering to a subject in need a pharmaceutical composition comprising a dicarboxylic acid ester.

Abstract: The present disclosure relates to bifunctional chemical epigenetic modifiers, and methods of making, kits and using the bifunctional chemical epigenetic modifiers. The bifunctional chemical epigenetic modifiers can include a FK506 molecule or derivative thereof, a linker and a bifunctional ligand. The bifunctional ligand can be a histone deacetylase inhibitor.

Abstract: A high-resolution dual-beam counter propagating optical-tweezers instrument was designed that can measure forces at <1 pN and one nanometer distance at a temporal resolution of 25 ?s with high accuracy and precision. Using the high-resolution optical-tweezers, time-dependent conformational switching and structural rearrangements in a single-molecule of the guanine aptamer were identified that follow a modified induced-fit model, where guanine remodels multiple barriers and triggers the receptor conformation rapidly to synchronize with the elongating transcriptional machinery for controlling gene regulation.

Abstract: The invention pertains to the field of adoptive cell immunotherapy. It provides with engineered immune cells comprising genetic alteration into genes which are involved into immune functions downregulation, especially in response to environment signals such as nutrients depletion. Such method allows the production of more potent immune cells in the context of tumors' microenvironment.

Abstract: A nanocarrier containing a combination of bioactive agents is provided. The nanocarrier allows for targeted delivery of the agents to cancer cells with minimized side effect.

Abstract: Fabricating a nanopore sensor includes depositing a first and second oxide layers on first and second sides of a sapphire substrate. The second oxide layer is patterned to form an etch mask having a mask opening in the second oxide layer. A crystalline orientation dependent wet anisotropic etch is performed on the second side of the sapphire substrate using the etch mask to form a cavity having sloped side walls through the sapphire substrate to yield an exposed portion of the first oxide layer, each of the sloped side walls being a crystalline facet aligned with a respective crystalline plane of the sapphire substrate. A silicon nitride layer is deposited on the first oxide layer. The exposed portion of the first oxide layer in the cavity is removed, thereby defining a silicon nitride membrane in the cavity. An opening is formed through the silicon nitride membrane.