Abstract: The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors as therapeutics and imaging agents. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in imaging methods and cancer therapy.

Abstract: The invention relates to a drug conjugate including a drug and a plant steroid. The drug conjugate may target the drug for intestinal cell delivery, and thus may be used to treat diseases, including intestinal diseases, or to affect intestinal metabolism. The invention therefore also relates to treating intestinal diseases and affecting intestinal metabolism with the drug conjugate.

Abstract: The present technology relates generally to oligolactic acid conjugates of paclitaxel, rapamycin, selumetinib, and other anticancer agents, micelle compositions containing such conjugates and methods of preparing and using such compositions to treat various cancers. Specifically, there are provided oligolactic acid conjugates wherein the oligolactic acid comprises 2 to 24 lactic acid subunits and is attached through an ester linkage to the oxygen of the 7-hydroxyl of the paclitaxel or paclitaxel derivative, the 40-hydroxyl of the rapamycin or rapamycin derivative, and the 2?-hydroxyl of the selumetinib or selumetinib derivative. Compositions comprising water and a micelle comprising a polylactic acid-containing polymer and the oligolactic acid conjugate may be readily prepared. Methods of inhibiting or killing cancer cells and treating paclitaxel, rapamycin, and/or selumetinib cancers are also provided.

Abstract: Provided herein are poly-1-hydroxymethylethylene hydroxymethyl formal (PHF)-based drug delivery systems. Also disclosed are methods of making antibodydrug conjugates and methods of treatment using these conjugates.

Abstract: The present invention provides an inhalable pharmaceutical composition comprising a glucocorticoid and a polyethylene glycol (PEG)-modified interleukin-2 for treating a respiratory disease. The invention further provides an application of a PEG-modified interleukin-2 for preparing a pharmaceutical composition for enhancing the efficacy of a glucocorticoid in treating the respiratory disease. The invention also provides a method for treating the respiratory disease.

Abstract: The present invention provides conjugates of deoxyribonuclease enzymes with water soluble polymers such as PSA having improved pharmacokinetic attributes. These modifications provide unexpectedly high levels of DNA hydrolytic activity in blood and other bodily tissues over the time due to markedly increased distribution phase and reduced clearance of DNase conjugates after delivery to blood circulation relative to the unconjugated compounds, while half-life and residence time of conjugates remains almost unchanged compared to the unconjugated DNase compounds. The compositions of the invention are used for parenteral treatment of diseases related to NET formation and the presence of extracellular DNA.

Abstract: Disclosed is a drug conjugate as a prodrug that is degraded by cathepsin B specifically expressed in tumor tissues to release doxorubicin. The drug conjugate can form self-assembled nanoparticles. In addition, the drug conjugate specifically responds to and is activated in tumor cells. Therefore, the use of the drug conjugate eliminates the incidence of side effects (for example, cell damage and apoptosis) during the course of cancer prevention or treatment.

Abstract: Disclosed herein are conjugates of a therapeutic compound and polypeptides, such as a conjugate of niclosamide and an elastin-like polypeptide. These conjugates may form nanoparticles through self-assembly, which improve the solubility, bioavailability, and pharmacokinetic profiles of the therapeutic compound. Also disclosed are methods for treating cancer, parasite infection, bacterial infection, viral infection, metabolic diseases, Type II diabetes, NASH, NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, and systemic sclerosis.

Abstract: The present invention relates to a composition comprising a lysosomal enzyme conjugated to a negatively charged scavenger receptor ligand. In some embodiments, the lysosomal enzyme is conjugated to the scavenger receptor ligand by way of a linker. The present invention also relates to a composition comprising lysosomal enzyme encapsulated by a liposome, said liposome externally comprising a negatively charged scavenger receptor ligand. The invention further encompasses a method of treating a lysosomal storage disease with the compositions listed above. The ionvention further encompasses a method of treating a lysosomal storage disease with an acylated, acetylated, or aconitylated lysosomal enzyme.

Abstract: A polycomplex comprising multiple Poly-lysine compounds, said Poly-lysine compounds being composed of at least one small molecule conjugated with a Poly-lysine. Compositions comprising the polycomplex and methods for treating an amyotrophic lateral sclerosis patient, the methods comprising administering to the patient one or more of the compositions.

Abstract: The present disclosure relates to antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs, and compositions comprising the antibody conjugates, including pharmaceutical compositions. Also provided are methods of producing the antibody conjugates and compositions as well as methods of using the antibody conjugates and compositions, such as in therapeutic and diagnostic methods.

Abstract: A composition for use in treating a condition associated with degeneration of articular cartilage and/or with subchondral bone loss is disclosed herein. The composition comprises a conjugate which comprises a polypeptide having attached thereto at least two polymeric moieties, at least one of the polymeric moieties exhibiting a reverse thermal gelation. Further disclosed is a composition comprising the aforementioned conjugate along with a hyaluronic acid, an anti-inflammatory agent, an analgesic, a growth factor, a blood fraction, a nucleic acid, and/or a cell, the composition being an aqueous composition which forms a hydrogel at a temperature in a range of from 32° C. to 37° C., as well as a method utilizing such a composition comprising a nucleic acid for effecting gene delivery.

Abstract: This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Abstract: Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1, block binding of PD-L1 to PD-1 and promote internalization and degradation of PD-L1 are provided. Antibodies that recognize specific epitopes on glycosylated PD-L1 protein and that exhibit the dual functions of both blocking the binding of PD-L1 to PD-1 and also facilitating the internalization of PD-L1 on cells are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for using such antibodies for the treatment of cancer, particularly PD-L1 positive cancer, are also provided.

Abstract: Provided herein are novel anti-CLDN antibodies and antibody drug conjugates (ADC), including derivatives thereof, and methods of using the same to treat proliferative disorders.

Abstract: The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, mutations in the serpentine receptor, Smoothened (SMO) are described, which result in resistance to a Hedgehog (Hh) pathway inhibitor, such as in medulloblastoma. Amino acid substitutions in conserved residues of SMO maintain Hh signaling, but result in the inability of the Hh pathway inhibitor, GDC-0449, to suppress the pathway. In some embodiments, the disclosure provides for novel mutant SMO proteins and nucleic acids and for screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.

Abstract: The present disclosure is directed to methods and compositions for the diagnosis and/or treatment of tumors, such as ocular tumors, using virus-like particles conjugated to photosensitive molecules.

Abstract: Provided are compositions and methods for promoting tolerance to auto-immune antigens. In general the compositions include quantum dots (QDs) that are in association with auto-immune peptide antigens. It is shown that QDs can be used to generate immunological tolerance by controlling the density of self-antigen on QDs. Peptide-QDs rapidly concentrate in draining lymph nodes, and co-localize with macrophages expressing scavenger receptors involved intolerance. Treatment with peptide-QDs reduces disease incidence 10-fold. The degree of tolerance and the underlying expansion of regulatory T cells correlates with the density of myelin molecules presented on QDs such that higher numbers of tolerogenic particles displaying lower levels of self-peptide are more effective for inducing tolerance than fewer particles each displaying higher densities of peptide. The disclosure is therefore relevant to promoting tolerance to antigens that are involved in a variety of autoimmune disorders.

Abstract: The invention provides powerful methods and compositions for designing, selecting, fine-tuning and optimizing polymer nanogel and other supramolecular assemblies for various properties including, for example, particle size, density and morphology, guest loading capacity and encapsulation stability, and dynamic release control.

Abstract: Provided herein are, inter alia, methods useful for delivering nucleic acids and kinase inhibitors to a cell. The methods provided herein include the delivery of therapeutic nucleic acids to cancer cells by contacting a cancer cell with a kinase inhibitor and a therapeutic nucleic acid. The methods provided herein are therefore, inter alia, useful for the treatment of cancer.

Abstract: Microbial type rhodopsins, such as the light-gated cation-selective membrane channel, channelrhodopsin-2 (Chop2/ChR2) or the ion pump halorhodopsin (HaloR) are expressed in retinal ganglion cells upon transduction using recombinant AAV vectors. Selective targeting of these transgenes for expression in discrete subcellular regions or sites is achieved by including a sorting motif in the vector that can target either the central area or surround (off-center) area of these cells. Nucleic acid molecules comprising nucleotide sequences encoding such rhodopsins and sorting motifs and their use in methods of differential expression of the transgene are disclosed. These compositions and methods provide significant improvements for restoring visual perception and various aspects of vision, particular in patients with retinal disease.

Abstract: A method for treating a patient suffering from a neuronal hypo-kinetic disease or a neuronal hyper-kinetic disease by modulating neuronal activity in the: internal globus pallidus (GPi), in the anterior motor thalamus and/or in the external globus pallidum (GPe) and/or in the subthalamic nucleus (STN) by utilizing suppressor and/or enhancer DREADDs is provided.

Abstract: The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules.

Abstract: The invention concerns a synthetic compound for enabling transfection of eukaryotic cells by means of an amphiphilic block copolymer which synthetic compound comprises a peptide residue having at least one targeting sequence and a nucleic acid binding sequence which nucleic acid binding sequence comprises or consists of at least four consecutive amino acid residues which are positively charged at pH 7.4, wherein the targeting sequence is any sequence that causes a direction of the sequence to a position or a structure inside or on the surface of eukaryotic cells, characterized in that the synthetic compound further comprises a hydrophobic moiety covalently linked to the peptide residue, wherein the hydrophobic moiety comprises or consists of lipoic acid residue, lipoamide residue, a tetradecyl residue, a cholesteryl residue, or a further peptide residue having a sequence with more than 40% amino acid residues with hydrophobic side chains.

Abstract: A method for in vivo RNA or protein expression is provided. The method includes introducing a double-stranded concatemeric DNA into a eukaryotic cell to generate a desired RNA or protein. The double-stranded concatemeric DNA includes a plurality of tandem repeat sequences, wherein each of the plurality of tandem repeat sequences comprises an expression sequence. The double-stranded concatemeric DNA comprises one or more phosphorothioated nucleotides, wherein a ratio of phosphorothioated nucleotides to total nucleotides in the double-stranded concatemeric DNA is at least 1:1600. A eukaryotic cell comprising an exogeneous, double-stranded concatemeric DNA comprising the plurality of tandem repeat sequences is also provided.

Abstract: Compositions include endonucleases of the family Cpf1 (CRISPR from Prevotella and Francisella 1); and at least one guide RNA (gRNA) complementary to a target sequence in a gene to specifically guide the Cpf1 endonuclease to the target site in a host cell in vitro or in vivo. Methods of treating a subject include the use of one or more of these 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: Compositions and methods are provided for inhibiting T cell mediated destruction of virally transduced, trangene containing cells.

Abstract: A compound having the formula of tetragadolinium [4,10-bis(carboxylatomethyl)-7-{-3,6,12,15-tetraoxo-16-[4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[{2-[4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl} amino)acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclo dodecan-1-yl]acetate wherein the stereochemistry at the chiral carbon of the four alanine substituents is selected from the group consisting of RRRR, SSSS, RSSS, RRSS, and RRRS stereoisomers, and racemic and diastereomeric mixtures of any thereof, or a tautomer, a hydrate, a solvate, or a salt thereof, or a mixture of same is described. The compounds may be used as an MRI contrast imaging agent.

Abstract: The present invention improves an existing contrast agent, especially, a T1 contrast agent, and adopts a strategy in which the T1 contrast material is partially coated on a support surface to which a hydrophilic functional group is exposed. The partial coating strategy adopted in the present invention improves both the stability and contrast performance of T1 contrast agent nanoparticles, and such a strategy leads to very interesting technical development.

Abstract: This invention relates to radioactive, bone-seeking, pharmaceutical methods, compositions and formulations that have a lower impurity profile, a longer shelf life, improved availability and are less expensive to prepare. The compositions of this invention can be conveniently prepared in a timely manner resulting in improved availability and delivery of the drugs to patients.

Abstract: The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof.

Abstract: The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in SPECT imaging methods.

Abstract: There is provided a radiolabelled peptide-based compound for diagnostic imaging using positron emission tomography (PET). The compound may thus be used for diagnosis of malignant diseases. The compound is particularly useful for imaging of somatostatin overexpression in tumors, wherein the compound is capable of being imaged by PET when administered with a target dose in the range of 150-350 MBq, such as 150-250 MBq, preferable in the range of 191-210 MBq.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level, reduced serum albumin level, elevated D-dimer or other coagulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others.

Abstract: Portable multifunctional device designed for sanitizing of inner and outer surfaces of shoes, sanitizing of air, water, household items and surfaces, treatment of skin and wound infection, nails fungus, cosmetic use, and detection of counterfeit currency. The device is able to perform all the above sanitizing, therapeutic and cosmetic functions that would otherwise be carried out by various different devices. The enhance functionality has been accomplished without alteration of any parts of the device. Apparatus utilizes light radiation in three diapasons: 100-280, 405-495, and 700-1064 nm and provides distant sanitizing. Apparatus comprises at least one module with a dual DC-AC power supply. Each module has a germicidal unit, retractable flexible shaft, shade, and housing. The flexible shaft allows positioning the germicidal units under different angle for uniform distant illumination. The device is suitable for household, traveling, and military use.

Abstract: A lighting device configured to deactivate MRSA bacteria in air in an environment, including a housing; a light-emitting diode (LED) configured to emit light having a wavelength of about 470 nm; a light converting phosphor coating; wherein a first component of the light emitted by the LED travels through the light converting phosphor coating without alteration, and a second component of light emitted by the LED is converted by the converting phosphor coating into light having a wavelength of greater than 500 nm; wherein the first component of the light has a minimum integrated irradiance of 0.01 mW/cm2; wherein the first component of the light emitted by the LED and the second component of light emitted by the LED mix to form a combined light, with the combined light being visible light; and means for directing the combined visible light to the air in the environment.

Abstract: The present disclosure is generally related to systems, methods and devices for providing ozone treatment of multiple medical devices including passageways. In particular the systems, methods and devices may attach to multiple medical devices and clean, disinfect and/or sterilize the inner space of the tubes, including the areas most prone for bacteria buildup. A multi-channel ozone treatment device has an ozone operating system and a distribution line that splits into a plurality of distribution channels to distribute ozone to a plurality of ozone ports in a gas-tight compartment. A multi-port connector unit for connecting to a plurality of passageways in the gas-tight compartment is further disclosed.

Abstract: An evaporation device for evaporating hydrogen peroxide is provided. The device comprises a housing body having at least two fluid channels arranged therein. The fluid channels are connected to each other to form a common fluid line between an inlet and an outlet. The housing body also includes and at least one heating element positioned within said housing body for heating said fluid channels. A first fluid channel, directly connected to the fluid inlet, is positioned relative to the at least one heating element such that its inner walls are heated to a first temperature, and a second fluid channel, being directly connected to the fluid outlet, is positioned relative to the at least one heating element such that its inner walls are heated to a second temperature. In some embodiments, said second temperature is higher than the first temperature.

Abstract: An aroma diffuser includes a liquid storage means, an enclosure provided with a mounting cavity, a gas supply means and a seal. The enclosure is covered on a liquid storage mean. The gas supply means and the liquid storage means are both aranged in the mounting cavity and communicate with each other. The gas supply means, the liquid storage means and the enclosure cooperate to form a gas return passage. The seal is arranged between the liquid storage means and the gas supply means, located in the gas return passage and sealingly abuts on the enclosure. The gas return passage can be blocked by the seal, aroma gas produced by the aroma diffuser is prevented from flowing back from the gas return passage into the gas supply means to reduce the concentration of the aroma gas released into the environment and thus to affect the use effect of the aroma diffuser.

Abstract: The humidifier disclosed herein may include a trap door for housing one or more chemically impregnated filter papers, referred to herein as “aroma pads,” containing aromatherapy oils and/or fragrances. In use, air is impregnated with the aromatherapy oils and/or fragrances, and the infused air is mixed with mist produced by the humidifier and disbursed into area served by the humidifier. The aroma pads may be housed in slots formed in the trap door, or, alternatively, in a tray inside an aroma compartment within the humidifier.

Abstract: A disinfecting apparatus may include a shelf securable to a wall; a mount configured to secure the shelf to the wall; at least one UV light source coupled to the shelf, the UV light being, configured to sanitize air and surfaces in close proximity to the UV light source; and a programmable controller being operatively coupled to the motion detector, the controller being configured to cause cause at least one of energization and de-energization of the UV light source upon a predetermined event. A method of safely disinfecting or sterilizing air and surfaces may include the apparatus and may further provide UV light in the range of 250-290 nm and interruption of the generation of UV light in response to the predetermined event.

Abstract: A disinfecting vanity mirror includes a substantially enclosed cabinet having top, a bottom, side and rear walls and a mirror panel as the front wall when mounted to form an enclosed space or chamber. The top and bottom walls include passageways to allow vertical air flow through the enclosed space to allow air to enter through the bottom wall to rise and exit through the top wall. Sources of UV light are provided both within and below the cabinet to sanitize the air moving upwardly through the plenum space and below the vanity mirror to expose interior surfaces and exterior surfaces below the cabinet such as sinks and countertops. A controller is programmed to interrupt or discontinue the generation of UV light when a motion detector senses motion in proximity to the mirror and/or in accordance with a programmed sequence of on and off times.

Abstract: The disclosed invention relates to a multifunctional photocatalytic module which includes a duct 10 having a flow cross section with long sides 11 and short sides 12; a suction port 13 and a discharge port 14, the suction port 13 and the discharge port 14 being informed on both ends of the duct; a fan 20 disposed close to the suction port in the duct, the fan introducing air from the suction port and apply pressure to the air toward the discharge port; a photocatalytic filter 40 disposed close to the discharge port in the duct; and a light source disposed between the photocatalytic filter 40 and the fan 20 and configured to radiate ultraviolet light toward the photocatalytic filter.

Abstract: Provided herein are methods for making foam materials and foam material products having a polyurethane foam matrix defining a plurality of pores, a hydrophilic agent retained within at least a portion of the pores for improving an absorption of the foam material, a salt retained within at least a portion of the pores in an amount sufficient to render the foam material isotonic, a surfactant retained within at least a portion of the pores in an amount sufficient to be released upon contact with a moist surface. Also provided herein are methods for making a multilayer foam by casting a second foam layer on a first foam layer substrate and compressing the second foam layer before the second layer is fully cured to form an interface layer in situ.

Abstract: A kit and a bioadhesive, comprising gelatin, alginate, montmorillonite and a coupling agent, which is characterized by rapid curing, optimal viscosity, high burst strength, flexibility, biocompatibility and biodegradability, is disclosed.

Abstract: A skin compatible component attachable to mammalian skin. The component is formed as a silicone matrix comprising a polyorganosiloxane derived silicone polymer and moisture control particulate distributed within the polymer network being configured to absorb moisture from the skin. The skin compatible component may be utilised as an ostomy wafer or flange to secure an ostomy appliance to the skin and in particular peri-skin.

Abstract: A non-tubular material for nerve regeneration induction, which can be used for the regeneration of a damaged part in a nerve, and which comprises: (A) a crosslinked form produced by crosslinking a low-endotoxin bioabsorbable polysaccharide having a carboxyl group in the molecule with at least one crosslinkable reagent selected from a compound represented by general formula (I) and a salt thereof via covalent bonds; and (B) a bioabsorbable polymer. R1HN—(CH2)n—NHR2 (I) [wherein R1 and R2 independently represent a hydrogen atom or a group represented by formula: —COCH(NH2)—(CH2)4—NH2, and n represents an integer of 2 to 18]. Thus, a medical material that can induce the regeneration of a damaged part in a nerve is provided.

Abstract: This invention concerns a method for the production of amorphous, nano- or microparticular materials based on inorganic polyphosphate (polyP) and calcium phosphate or calcium carbonate that show osteogenic activity. In one aspect of the invention, the inventor shows that amorphous calcium polyphosphate (Ca-polyP) microparticles can be used for biological functionalization of titanium alloy surfaces. The inventive method allows the fabrication of a durable and stable, almost homogeneous and morphogenetically active Ca-polyP layer on titanium oxidized Ti-6Al-4V scaffolds that supports the growth and enhances the functional activity of bone cells, in contrast to biologically inert non-modified titanium surfaces. A preferred aspect relates to the formation of amorphous calcium phosphate (CaP) particles in the presence of low concentrations of sodium polyP. This material causes a strong upregulation of the expression of proteins involved in bone formation.

Abstract: The present invention relates to a biomaterial comprising adipose-derived stem cells (ASCs), a ceramic material and an extracellular matrix. In particular, the biomaterial according the present invention secretes osteoprotegerin (OPG), and comprises insulin-like growth factor (IGF1) and stromal cell-derived factor 1-alpha (SDF-1?). The present invention also relates to methods for producing the biomaterial and uses thereof.