Abstract: A method for reducing the viscosity of a pharmaceutical formulation is provided that utilizes a viscosity-reducing concentration of an excipient selected from the group consisting of the n-acetyl arginine, n-acetyl lysine, n-acetyl proline and mixtures thereof in combination with a therapeutiv protein. A stable pharmaceutical formulation is also provided.

Abstract: The present disclosure relates to chimeric antigen receptors (CARs), which bind to Globo series antigens (e.g. Globo H, SSEA-3 or SSEA-4), including an antigen-binding fragment (Fab) or a single-chain variable fragment (scFv). Further, the present methods are also provided for administering CARs to a subject in an amount effective to inhibit cancer cells.

Abstract: Disclosed are combination therapies for cancer utilizing the leverage of the adaptive immune system through chimeric antigen receptor (CAR) T cells, combined with leveraging the innate immune system by using CAR-macrophages (CAR-M) and CAR-natural killer (NK) cells. In some embodiments, the invention teaches the initial modification of the tumor microenvironment by administration of CAR-M and CAR-NK. The alteration of the tumor microenvironment results in reduction of barriers for CAR-T cells to enter the tumor, which allows for efficacy of CAR-T in treatment of solid tumors. In some embodiments adjuvant immunotherapies are utilized to expand immunological attack such as addition of complement, immunotherapeutic antibodies, chemotherapy and radiotherapy approaches.

Abstract: The present disclosure relates to cells capable of co-expressing one or any combination of T cell receptors (“TCR”), CD8 polypeptides, interleukin 12 (IL-12) polypeptides, interleukin 15 (IL-15) polypeptides, and/or interleukin 18 (IL-18) polypeptides, and the use thereof in adoptive cellular therapy (“ACT”). The present disclosure further provides for modified CD8 sequences, IL-12 sequences, IL-15 sequences, IL-18 sequences, vectors, compositions, transformed T cells, and associated methods thereof.

Abstract: Provided is a method of reducing a number of viable microbes, including contacting microbes with an antibiotic compound and applying pulses of electricity having a duration of between about 50 nanoseconds and about 900 nanoseconds. The pulses of electricity may have an intensity between about 20 kV/cm and about 40 kV/cm. The pulses of electricity may be applied at a frequency of between about 0.1 Hz and about 10 Hz. The microbes may be a gram-negative or a gram-positive strain of bacteria and the antibiotic may be applied at a concentration for a duration, wherein applying the antibiotic to the strain at the concentration for the duration does not reduce a viable number of bacteria of the strain as much, or at all, when the pulses of electricity are not also applied.

Abstract: Disclosed herein are lipid compositions comprising a cationic lipid of formula (I), a neutral lipid, a sterol and a PEG or PEG-modified lipid, wherein formula (I) is (F). Also disclosed are methods of producing the cationic lipid of formula (I).

Abstract: The invention relates to oral administration of biological actives, in particular of insulin, comprising the use of a cross-linked starchy material as a delivery system.

Abstract: The present invention provides hepcidin analogues with improved in vivo half lives, and related pharmaceutical compositions and methods of use thereof.

Abstract: The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3: wherein R1, R2, R3, R4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders.

Abstract: The present disclosure provides a class of conjugates of general formula (X), a class of TLR9 agonist derivatives, such as formula (I), (XX), and (XXI), certain diastereomers of STING agonists, a class of STING agonist derivatives, such as formula (XXVIV), a class of heterocyclic compounds of general formula (II), a class of heterocyclic compounds of general formula (III), as defined herein. A1, A2, T, Z1, Z2, Z3, b1, and b2, in formula (X) are defined herein. The conjugate provides unique properties that are based upon the properties of the therapeutic agents that are part of the conjugate. Also provided are methods of synthesis and use of compounds.

Abstract: Disclosed herein, inter alia, are compounds and methods of using the same for modulating the activity of mTORC1.

Abstract: The invention generally relates to the design and production of drug conjugates, and specifically conjugates of antibiotic agents to cationic and non-cationic molecular transporters.

Abstract: Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are compounds having a DNA damage-binding protein 1 (DDB1) binding moiety. Some such embodiments include a linker. Some such embodiments include a target protein binding moiety. Further provided herein are ligand-DDB1 complexes. Further provided herein are in vivo modified DDB1 proteins.

Abstract: The present invention relates to a protein conjugate comprising polyubiquitin, a carrier linked to the polyubiquitin, and two or more biomolecules linked to the polyubiquitin or the carrier. In addition, the present invention relates to a pharmaceutical composition for preventing or treating non-alcoholic steatohepatitis (NASH), fatty liver, liver fibrosis, cirrhosis, liver cancer, obesity, and diabetes, comprising the protein conjugate that comprises two or more biomolecules.

Abstract: Provided herein are antibody-drug conjugates, for example, a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.

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: 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 inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Abstract: The present disclosure relates to a linker molecule for targeting molecule-drug conjugate, and the corresponding conjugate, the preparation and use thereof.

Abstract: The present invention describes a uPAR (urokinase Plasminogen Activator Receptor)-targeting conjugate comprising: —a fluorophore; —a molecule binding to the receptor; and—a linker group which covalently links the fluorophore to the molecule binding to the receptor, said linker group either being part of the molecule binding to the receptor or being a separate component of the uPAR (urokinase Plasminogen Activator Receptor)-targeting conjugate; wherein the uPAR (urokinase Plasminogen Activator Receptor)-targeting conjugate has a pharmacokinetic profile where a human TBR (tumor-to-background ratio) of at least 1.1 is reached within 3.5 hours post administration and where a human TBR of at least 1.5 is maintained at least 30 minutes before decreasing below 1.5, and wherein the uPAR-targeting conjugate is a human uPAR-targeting conjugate.

Abstract: This invention discloses a natural polyphenols-based, multi-stage porous hydrogel sustained release drug delivery system, which relates to the field of drug delivery. It consists of the hydrogel matrix and the supramolecular filler, which is a complex of natural bio-based polymers and metal ions. The natural bio-based polymer can be natural polyphenols, dopamine or its derivatives, polysaccharide biomass, or protein biomass. The hydrogel matrix can be chitosan, carboxymethyl chitosan, sodium alginate, carboxymethyl cellulose, hyaluronic acid, collagen, gelatin, or agarose. The metal ion can be one of the cations of Al, Fe, Zn, Mn, Ni, Co, or V. By this invention, the supramolecular filler based on natural bio-based polymer can form in situ in the hydrogel, to regulate the pores of the hydrogel and interact with different drugs, thus adjusting the drug release rate.

Abstract: Described herein are liposome-based nanocarriers that selectively target bone marrow, minimize tumor delivery, and maintain high drug concentrations in bone marrow when compared to conventional systemic delivery. The composition of the liposome-based nanocarriers may also be tuned to selectively target lymph nodes and other reticuloendothelial system organs (e.g., spleen, e.g., livers. Also described herein are methods of imaging and mapping the bone marrow and/or other reticuloendothelial system organs using the described liposome-based nanocarriers. These methods provide high resolution non-invasive and quantitative imaging via PET, which offers advantages over conventional imaging/tracking methods. Furthermore, in certain embodiments, the liposome-based carriers are used to stabilize and deliver radioprotectant/free radical scavenger drugs to the bone marrow, thereby protecting the bone marrow from subsequent radiation exposure, thereby limiting the adverse impact of radiation exposure of the individual.

Abstract: Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.

Abstract: The present invention provides compositions comprising a recombinant AAV and one or more pharmaceutically acceptable excipients. The compositions have improved stability and shelf life as compared to other AAV compositions.

Abstract: An isolated recombinant parvovirus vector comprising a synthetic enhancer comprising plurality of enhancer sequences operably linked to a promoter, and methods of using the vector, are provided.

Abstract: The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

Abstract: The invention provides a nucleic acid molecule comprising a gene encoding a fusion protein of a ligand and a protein having physiological activity, to be used for expressing the fusion protein in cells, tissue or the body. The invention further provides a nucleic acid molecule comprising the fusion protein-encoding gene, which is in the form of a plasmid, in a form encapsulated in a recombinant virus virion, or a form encapsulated in liposomes or lipid nanoparticles. The invention further relates to the use of a medicine which is a nucleic acid molecule comprising the fusion protein-encoding gene.

Abstract: The present application provides materials and methods for treating a patient with one or more conditions associated with SCN10A whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of SCN10A gene in a cell by genome editing.

Abstract: Disclosed herein are therapeutic agents capable of increasing the expression level of ELOVL2. Also described herein are therapeutic agents that reduce or slow an aging phenotype. Methods for treating age-related eye diseases or conditions are also provided. Methods for treating an age-related eye disease or condition in a subject by administering one or more therapeutic agents are provided.

Abstract: The present invention provides: an MRI contrast agent for detecting cartilage damage, which comprises 17O-labeled water; and a method and a program for detecting cartilage damage using the contrast agent. According to the present invention, it becomes possible to detect a damage in a cartilage, particularly a minor damage in the surface layer of a cartilage which has been difficult to detect so far, by using 17O-labeled water as a contrast agent.

Abstract: This invention relates to the detection of the diseases by using Chemical Exchange Saturation Transfer (CEST)—Magnetic Resonance Imaging (MRI). Previously, there was no way to use CEST MRI to early detect and map the agents bind to amyloid beta protein, tau protein, alpha-synuclein protein in neurodegenerative diseases, and inflammation in many diseases such as neurodegenerative diseases. The exogenous agents can be used to produce MRI contrast, such as agents contain exchangeable protons such as hydroxyl, amine, and amide protons, and thereby provide imaging and mapping for detection of the amyloid beta protein, tau protein, alpha-synuclein protein, and aggregation proteins in neurodegenerative diseases and inflammation in many diseases such as neurodegenerative diseases, and other inflammatory diseases.

Abstract: The present invention provides iron oxide magnetic particles containing iron oxide and MXn, wherein M as a transition metal containing electrons in a 5d orbital on the periodic table includes one or more selected from the group consisting of Hf, Ta, W, Re, Os, Ir, Pt, Au, and Hg, X includes one or more selected from the group consisting of F, Cl, Br, and I, and n is an integer of 1 to 6.

Abstract: The present invention relates to compounds of the Formula (1) and pharmaceutically acceptable salts thereof, wherein M3+ is as defined herein, and their use as cancer diagnostic or imaging agents.

Abstract: The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula: wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

Abstract: The present invention discloses complex for PET imaging in patients with Cushing's syndrome dependent on secretion of a hormone called ACTH from pituitary. This will help to distinguish Cushing's disease due to pituitary tumor (adenoma) or due to tumor of origin other than pituitary (ectopic Cushing's syndrome). It will also be helpful to delineate ACTH producing pituitary adenoma (corticotropinoma). More particularly the work disclosed an imaging complex comprising radiolabelled analogue of desmopressin for PET imaging to localize pituitary adenoma.

Abstract: An X-ray irradiation system includes a support for an object requiring decontamination, a first source of irradiation directed to a top side of the object; a second source of irradiation directed to a bottom side of the object; and a controller configured to control a dose rate and a time of each of the first source and the second source to optimize decontamination of the object. A method of irradiating an object is further disclosed.

Abstract: A method is for sterilization of flexible bags containing human plasma protein solution with electron beam. The method includes emitting at least one electron beam with energy between 400 and 500 keV. After approximately 10 nsec to 1.5 sec, a second electron beam pulse is emitted with an energy of at least 4 MeV.

Abstract: The present invention relates to a shelf (10) for a UV-C disinfection chamber (12) comprising at least one UV-C light source (24) adapted to emit UV-C radiation (22) inside the UV-C disinfection chamber, the shelf comprising: a metal mesh shelf plate (14); and at least one optical element (26), wherein each optical element of the at least one optical element is adapted to locally modify the UV-C radiation relative to an object (28) supported by the shelf in conjunction with the optical element when the shelf is placed inside the UV-C disinfection chamber.

Abstract: A plasma generator generates atmospheric pressure, low temperature plasma (cold plasma), and includes a thin plate-like first electrode defining a planar bottom surface. A thin plate-like second electrode defines a planar top surface. The second electrode opposes the first electrode, such that the bottom surface of the first electrode faces the top surface of the second electrode. A first dielectric layer is disposed on the bottom surface of the first electrode, and a second dielectric layer is disposed on the top surface of the second electrode. A spacer supports the first and second electrodes to define a predetermined gap between the first and second dielectric layers. A power supply supplies electrical power to the first and second electrodes at a predetermined voltage and frequency, such that, based on the predetermined gap between the first and second dielectric layers, cold plasma is generated.

Abstract: Described herein is a nonwoven wipe comprising a plurality of polyolefin fibers, wherein the plurality of polyolefin fibers have an average fiber diameter of at least 200 nm and at most 3.5 micrometers, and wherein the plurality of polyolefin fibers have a basis weight of at least 20 and no more than 100 grams per square meter. Such nonwoven wipes can be used with an aqueous solution, optionally comprising an active ingredient, to decontaminate a surface. Also disclosed herein in a decontamination kit providing the same and a method of decontaminating a surface.

Abstract: Waste processing chamber operates in a loading mode, a processing mode and an unloading mode. In the processing mode, an environment inside the processing chamber disinfects particles of medical waste using ozone. The processing chamber includes an inlet to receive the particles. In the processing mode and unloading mode a hermetic seal is provided between the environment inside and an environment outside of the processing chamber. An outlet extracts the particles from the processing chamber and provides a hermetic seal between the environment inside and the environment outside of the processing chamber. A particle transporting arrangement stirs the particles to move the particles to the outlet for extraction. Sensors measure characteristics of the sealed environment inside the processing chamber. The processing chamber is fluidly coupled to or includes a generator to generate ozone and to maintain a target concentration level of ozone of the environment inside the processing chamber.

Abstract: The invention relates to an isolator (10) for processing medical substances and a method for decontamination of an isolator (10).

Abstract: A hydrogen peroxide vapor vaporizer, which is used in a sterilizer that sterilizes by using hydrogen peroxide vapor generated by vaporizing a hydrogen peroxide solution, comprises: a body part formed in the shape of a hollow column; a vaporization part which is provided at one side of the inside of the body part and has a predetermined capacity to accommodate a predetermined hydrogen peroxide solution; support parts for supporting the vaporization part to provide same to be spaced a predetermined distance apart from the inside of the body part; a heating part which is provided at one side of the vaporization part to heat the vaporization part; and a discharge part which is provided at the upper portion of the body part to induce discharging of the hydrogen peroxide vapor vaporized in the vaporization part.

Abstract: A system for disinfecting an enclosed chamber may include a housing, an inlet and an outlet carried by the housing to be connected in an airflow path with the enclosed chamber, and a blower carried by the housing and connected to the airflow path between the inlet and outlet and configured to circulate air through the airflow path. The system may further include a disinfectant fog generator configured to introduce a disinfectant fog into the airflow path at room temperature from a disinfectant fluid, and a controller configured to operate the disinfectant fog generator and a dehumidifier coupled to the airflow path during a treatment phase.

Abstract: Proposed is a disinfection device for automatically disinfecting a transport container intended for transporting one or more inspection objects through an inspection apparatus and non-destructively inspecting them in the inspection apparatus, the disinfection device including: an input point connected to a pick-up point, an output point connected to a lay-up point, and at least one return device extending from the input point to the output point, and at least one automatic disinfection device arranged at the return path for disinfecting the emptied transport containers.

Abstract: Provided herein is a catheter system that includes an intravenous catheter assembly including a catheter defining a lumen extending between a distal end and a proximal end of the catheter and an access connector configured to provide access to the lumen of the catheter. The catheter system also includes a disinfecting probe coupleable to the access connector, with the disinfecting probe including a housing having a proximal end and a distal end, a lighting system disposed at least partially within the housing and configured to emit a disinfecting ultraviolet light, and an advancement member configured to advance a portion of the lighting system beyond the distal end of the housing and into the catheter, responsive to movement of the advancement member with respect to the housing, wherein the disinfecting ultraviolet light disinfects the lumen of the catheter upon being advanced therein by the advancement member.

Abstract: A biological indicator reader is provided for reading a plurality of biological indicators to determine the effectiveness of at least a sterilization process. Each biological indicator is configured to exhibit fluorescence when the sterilization process has failed. Each reader comprises a housing having a plurality of biological indicator holders, a heater coupled to the housing and configured to heat the plurality of biological indicator holders to a preselected temperature to incubate the biological indicators, a UV light emitter configured to emit UV light through a first aperture on the side of each holder and an optical detector positioned under a second aperture on the bottom of the biological indicator holder, the optical detector configured to detect fluorescence intensity indicating the effectiveness of the sterilization process. A method of using the biological indicator reader is provided. A biological indicator system is also provided.

Abstract: A biological indicator reader is provided for reading a plurality of biological indicators to determine the effectiveness of at least a sterilization process. Each biological indicator is configured to exhibit fluorescence when the sterilization process has failed. Each reader comprises a housing having a plurality of biological indicator holders, a heater coupled to the housing and configured to heat the plurality of biological indicator holders to a preselected temperature to incubate the biological indicators, a UV light emitter configured to emit UV light through a first aperture on the side of each holder and an optical detector positioned under a second aperture on the bottom of the biological indicator holder, the optical detector configured to detect fluorescence intensity indicating the effectiveness of the sterilization process. A method of using the biological indicator reader is provided. A biological indicator system is also provided.

Abstract: Provided is a candle warmer with a height adjustment function, and more particularly, to a candle warmer with a height adjustment function that adjusts a height between a candle and a heating element, thus allowing a user to flexibly correspond to various forms or types of scent-releasing candles used and allowing a scent release effect to last by efficiently melting a candle even when the candle melts and shortens.

Abstract: The present utility model discloses a volatilization device with a novel structure, which includes a bottle body for storing aromatic liquid, a cover body movably connected to an opening of the bottle body, a base with a semi-open structure, and a diffusion sheet, wherein the diffusion sheet is disposed in the base, and a permeable membrane is disposed on the opening; and when in use, the opening is located in the base, and the permeable membrane is abutted against the diffusion sheet. The present utility model has the beneficial effects that the structure is simple, and unnecessary parts are discarded, so that the production cost is minimized; furthermore, an upside-down structure ensures that liquid can penetrate and volatilize completely; different diffusion rates can be achieved by using permeable membranes of different permeabilities; and in addition, decorations can be added in the bottle body to further improve the added value.

Abstract: The diffusion device comprises a refill (1) in which liquid containing the volatile substances is housed, the refill (1) comprising: a hole (2) for the passage of the liquid; a sealing element (3) movable between a closed position in which it prevents the passage of the liquid and an open position in which it allows the liquid to pass through the hole (2); and an elastic element (4) that presses the sealing element (3) into its closed position, wherein the sealing element (3) comprises a housing (8) for housing an activation element (7) that moves the closure element (3) from the closed position to the open position against the action of the elastic element (4). It permits to provide a device that only works when the refill is original and is inserted in the correct position.