Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions by modulating (e.g., reducing) the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C.

Abstract: The present invention relates to compounds of Formula (I?) and Formula (I), and pharmaceutically acceptable salts or tautomers thereof. Also disclosed are compositions, combination therapies, kits, uses, and methods. Exemplary uses include treating diseases and disorders including cancers (e.g., hemopoietic cancers (e.g., leukemia, lymphoma, multiple myeloma)), inflammatory diseases (e.g., erythema nodosum leprosum, arthritis, Crohn's disease, colitis, inflammatory bowel disease), and autoimmune diseases (e.g., pulmonary fibrosis, systemic lupus erythematosus).

Abstract: The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.

Abstract: Psychedelic drug (PD) polymer conjugates having a general structure PD-(X-Poly-T)n, wherein PD is a CNS active psychedelic drug targeting serotonergic receptors, with possible affinity also for other receptors. (X-Poly-T) is, independently for each occurrence, hydrogen or the moieties are, independently: X is a stable (enzymatically and/or hydrolytically under physiological conditions) linker comprising a covalent bond or a chain of atoms that covalently attaches a small molecule 5-HT receptors agonist drug moiety to the Poly derivative. Poly is a covalently bonded chain of repeating monomer units that form a polymer or an oligomer backbone of synthetic or natural origin. T is terminal group of Poly and is represented by any suitable chemical group which, depending upon preference, is unreactive or reactive with other chemical moieties, or has a targeting property. N is an integer comprised between 1 and 6.

Abstract: The present disclosure is directed to cell penetrating peptides, including cyclic cell penetrating peptides with high cytosolic delivery efficiency and reduced toxicity that are able to effectively deliver cargo inside a cell to treat a variety of conditions and diseases.

Abstract: The present invention features compositions and methods for the localization and concentration of various growth factors (e.g., vascular endothelial growth factor (VEGF), or an angiopoietin-1 (ANG1) protein, or an angiopoietin-2 (ANG2) protein) within a scaffold structure. The present invention may also be used to promote the rebuilding of vasculature on de-celled organs (e.g., a kidney) or artificial organs.

Abstract: Disclosed herein are methods for treating head and neck squamous cell carcinoma (HNSCC) in a subject in need thereof, comprising administering IL-2 conjugates in combination with one or more additional agents.

Abstract: The present invention relates to compounds capable of binding to the PDZ domains of PSD-95 and their medical use as inhibitors of protein-protein interaction mediated by PSD-95.

Abstract: The present disclosure provides anti-CD37 antibodies and anti-CD37 antibody-maytansine conjugate structures. The disclosure also encompasses methods of production of such antibodies and conjugates, as well as methods of using the same.

Abstract: The present application relates to a method for preparing an antibody drug conjugate and an application thereof. Specifically, the present application relates to a compound, or a tautomer, mesomer, racemate, enantiomer, and diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt, prodrug or solvate thereof, as well as a method for preparing the compound and related antibody drug conjugates and use thereof in the preparation of drugs for the treatment of cancers.

Abstract: The present invention provides Polar units, Linker intermediates, Linkers, Drug-Linkers and Conjugates thereof.

Abstract: [Problems] To provide a technique for efficiently incorporating an agent having to function in muscle tissue, which is not sufficiently incorporated into muscle tissue when administered in body, into muscle tissue, particularly muscle tissue composed of skeletal muscle or cardiac muscle. [Solution] A conjugate of an anti-human transferrin receptor antibody and an agent, wherein the agent is a biologically active agent that should function in muscle tissue, e.g., a lysosomal enzyme such as acid ?-glucosidase, ?-galactosidase A.

Abstract: The present invention relates to novel anti-TPBG antibody comprising Fc silencing mutations such as leucine (L) to alanine (A) substitution at the position 234 and 235 (LALA mutations), antibody-drug-conjugates (ADCs) based thereon as well as to therapeutic methods and uses thereof, particularly in relation to cancer treatment.

Abstract: The present application relates to a preparation method for an antibody-drug conjugate and an application, and in particular, to a compound, or a tautomer, mesomer, racemate, enantiomer, and diastereomer, or mixture thereof, or a pharmaceutically acceptable salt, prodrug or solvate thereof, a preparation method for the compound and related antibody-drug conjugates, and a use of the same in the preparation of drugs for the treating cancer.

Abstract: The present disclosure relates to the development of drug delivery systems comprising single domain antibodies (sdAbs). For this purpose, antibody-drug conjugates (ADCs) are provided with high selectivity and efficiency to be used advantageously in cancer therapy, and a drug-delivery system targeting the central nervous system (CNS) pathologies. The ADC molecules developed for therapy, namely for cancer therapy are obtained from rabbit derived sdAbs comprising a potent cytotoxic payload, a SN38 small molecule conjugated with the free exposed cysteine at position 80, 23 or 88 of the VL framework. The drug delivery systems developed targeting the BBB endothelial cell receptors of the central nervous system (CNS) comprise rabbit derived single-domain antibodies (sdAb) conjugated at the surface of liposomes encapsulated with a suitable drug enabling an efficient blood-brain barrier (BBB) translocation. The respective process of production is also herein disclosed.

Abstract: The present invention relates to anti-matriptase antibodies and immunoconjugates of anti-matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase.

Abstract: The present invention is related to a brain targeted drug delivery system (DDS). The DDS penetrates the blood brain barrier and delivers the drug by using extracellular vesicles (bEVs) derived from brain vascular endothelial cells. The present invention provides a composition for enhancing PDT efficacy comprising bEV loaded with TPP-Ce6. The bEV of the present invention penetrates the BBB effectively without cytotoxicity, and the bEV loaded with TPP-Ce6 is selectively absorbed by brain tumor cells, and releases TPP-Ce6 under a light condition, and the TPP-Ce6 accumulates preferably in mitochondria first. This invention is expected to enhance therapeutic efficacy of PDT and minimize side effects in the treatment of brain tumors.

Abstract: Multifunctional nanoparticles incorporate an ERS inducer (p97 inhibitors) and immunotherapeutics (immune-modulating miR or aptamer plus immunoadjuvants) to address the poor aqueous solubility and toxicity associated with p97 inhibitors and immunotherapeutics while also enhancing the immune activation of these therapeutics. The nanoformulation offers several advantages, such as pH-sensitivity, self-detachable coating, active targeting, and intracellular localization in tumors, and has the potential to overcome the limitations of systemic administration, such as the degradation of nucleic acid therapeutics and toxicities associated with ERS inducer.

Abstract: A method of constitutively expressing a bacterial dinucleotide cyclase in a mammalian cell is provided. The method comprises transfecting the mammalian cell with a transgene encoding the bacterial dinucleotide cyclase and subjecting the mammalian cell to suitable growth conditions. In an embodiment, the bacterial dinucleotide cyclase is expressed in a tumour or cancer cell and is useful to treat cancer.

Abstract: Circular RNA, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises post splicing group I in iron fragments, spacers, an IRES, optional duplex forming regions, and more than one expression sequence. In some embodiments, the expression sequences are separated by one or more polynucleotide sequences encoding a cleavage site. In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

Abstract: A method of treating or preventing a neurodegenerative disease or disorder such as Alzheimer's disease, or Down syndrome is described. The method includes administering a therapeutically effective amount of a CsA-type drug and/or an INDY-type to a subject in need thereof. Methods of identifying a neuromodulating drug using zebrafish larvae are also described.

Abstract: Described herein are cyclophanes, compositions, and methods for live cell imaging. The cyclophanes comprise an ordered, cyclic arrangement of a chromophore, a first linker unit, a molecular strut, and a second linker unit. The compositions are capable of being taking up by cells and resist photobleaching under live-cell imaging conditions.

Abstract: Disclosed are a polymer-modified magnetic nanomaterial (polymer-modified MNM), and a preparation method and use thereof. Provided is the polymer-modified magnetic nanomaterial, including the following structure: a polymer is attached to or coated on a surface of a magnetic nanomaterial (MNM) to form the polymer-modified MNM that is positively charged, wherein the polymer is a cationic polymer, the MNM has a core-shell structure, a core is a magnetic nanoparticle (MNP), and a shell is a modified layer and the modified layer is attached to or coated on a surface of the MNP to form a modified layer-compounded MNP; and a mass ratio of the polymer to the MNM in the polymer-modified MNM is in a range of 1:10 to 20:1.

Abstract: A contrast agent for MRI imaging diagnostics. The contrast agent is comprised of a nano-fuel cell coupled to at least one ligand for specific binding to a cell membrane. An imaging method for the visualisation of tumor cells using the contrast agent and a method for non invasive treatment of tumor cells using the contrast agent.

Abstract: Method and apparatus for the generation and isolation of radionuclides comprising the steps of providing a radioactive gas, allowing the radioactive gas to decay to form charged daughter radionuclides, providing a liquid in contact with the gas, subjecting the charged daughter radionuclides (16) to an electric field between two electrodes (5,6), thereby absorbing the charged daughter radionuclides (16) in the liquid, and isolating the liquid comprising the charged daughter radionuclides (16).

Abstract: An alpha radiolabeled gastrin analogue is used in peptide receptor radionuclide therapy (PRRT) applications. In particular, an alpha radiolabeled gastrin analogue, which exhibits excellent biodistribution and therapeutic efficacy while toxicity for healthy tissues is prevented and/or reduced. The alpha radiolabeled gastrin analogue is used in methods of treating cholecystokinin (CCKB) receptor positive diseases.

Abstract: Devices and methods for disinfecting a medical probe are provided. In an aspect, a disinfection device for a medical probe includes a container having an opening, a plurality of ultraviolet (UV) light emitters disposed in the container and to emit UV light to disinfect a surface of the medical probe, and a probe holder to hold the medical probe apart from the plurality of electromagnetic wave emitters when at least a portion the medical probe is inserted into the opening of the container and the probe holder.

Abstract: A disinfection system is provided. The disinfection system may utilize ultraviolet light and/or ozone for disinfection of infected tissue. For example the system may involve an endoscopic ultraviolet light to disinfect lung tissue. In another aspect, the system may involve a ventilator which provides ozone in small doses to disinfect the tissue. Combinations and variations are further disclosed.

Abstract: The invention relates to a disinfection lighting device (10) comprising a first light source (14), wherein the first light source (14) comprises a solid-state light source, wherein the solid-state light source comprises one or more light emitting diodes (14a, 14b), lasers and/or superluminescent diodes; wherein the first light source (14) is configured to generate first light source light having a first spectral power distribution, wherein the first spectral power distribution comprises first light source light (140) in the UV wavelength range and/or visible wavelength range, a second light source (13), wherein the second light source (13) is configured to generate second light source light (130) having a second spectral power distribution different from the first spectral power distribution, wherein the second spectral power distribution comprise in the UV wavelength range, wherein the second light source (13) is arranged at a distance D from the first light source (14), the second light source (13) comprise

Abstract: The disclosure provides a plasma module, a disinfection and sterilization apparatus, and an air duct assembly. An outer surface of the plasma module at least includes a domed surface and a flat surface, an edge of the domed surface being in sealed connection with an edge of the flat surface. The plasma module further includes a plasma emission probe, at least a part of the plasma emission probe being exposed outside an outer surface of the domed surface; and a plasma generator, the plasma generator being arranged inside the plasma module, and the plasma generator being electrically connected to a part, located inside the plasma module, of the plasma emission probe. By using the plasma module, the wind resistance is reduced, and the flow efficiency of positive and negative ions generated by the plasma generator is improved, so that the sterilization efficiency is increased.

Abstract: Disclosed herein are biological indicators suitable for use in a liquid-chemical sterilization process that may be conducted by an automated endoscope reprocessor. The biological indicator may include one or more ports for introducing and removing a liquid chemical sterilant therefrom. The biological indicators may include features, such as a declivity leading to a port opening or a pipette, that may assist in transferring the liquid chemical sterilant. The system may additionally include a holder having features that facilitate use of the system and biological indicators.

Abstract: A plant for treating objects comprising a plurality of pre-treatment stations, a plurality of pick-up benches for picking up baskets containing pre-treated objects, a plurality of treatment machines, and at least one unmanned shuttle which is mobile between the pick-up benches and respective inlet apertures of the treatment machines. The plant comprises a supervision system provided with visual acquisition means connected to a central control unit.

Abstract: A container-sterilizer includes a rotating body and a manifold which are configured to rotate coaxially and integrally with a rotational shaft which is rotatably supported by a fixed member. Sterilizing nozzles to inject a sterilizing agent are connected to the manifold. A penetrating member attached to the fixed member is provided in the rotational shaft to pass through the rotational shaft to the manifold. The manifold has supply openings communicating with the sterilizing nozzles. The penetrating member has a shielding member which is provided in the manifold and which is configured to supply the sterilizing agent in the manifold to some supply openings among the plurality of sterilizing nozzles.

Abstract: Disclosed herein are disinfection inserts comprising a fiber optic and a polymer surrounding at least a portion of the fiber optic (and methods of making and using the same). The polymer comprises a NO donor molecule that releases NO upon illumination of the polymer by the fiber optic. The disinfection inserts can be inserted into tubing, catheters, and/or extracorporeal devices and illuminated to release NO from the polymer. The released NO inactivates pathogens on or within the tubing, catheter, and/or extracorporeal device. The disinfection insert can be configured for removable attachment to the tubing, catheter, and/or extracorporeal device, such that it can be periodically replaced. Furthermore, the disinfection insert can be placed in optical communication with a controllable light source. The controllable light source can be coupled to a light source controller. The intensity and wavelength of the light can be varied to change the flux of NO.

Abstract: To provide a sterilizer gasification apparatus that gasifies a sterilizer with reliability, improves the concentration of the sterilizer in the gas and is compact and a sterilizer gasification method. A helical metal pipe that meets at least one of conditions that a pitch of the helical pipe is equal to or greater than 1.0 mm and equal to or smaller than 30.0 mm and that an angle of the helix is greater than 0 degrees and equal to or smaller than 30 degrees with respect to a plane perpendicular to a central axis of the helix, a solidified molten metal layer in which the helical metal pipe is embedded in a casting process, a heating body that heats an outer surface of the solidified molten metal layer, and a nozzle that is at one end of the helical metal pipe and sprays a sterilizer into the helical metal pipe are provided.

Abstract: A battery-powered tracking component may be attached to a sterilization case. The tracking component may collect, store and transmit usage information associated with the sterilization case. The supplying of power to the tracking component may be temporarily stopped during autoclave processes. As the high temperatures and pressurized steam of autoclave processes may drain an active battery, the lifespan of the battery may be elongated by deactivating the battery during the autoclave processes. A temperature sensor may detect when the temperature of the sterilization case rises above a threshold indicating a start of the autoclave process, and when the temperature of the sterilization case falls below a threshold indicating an end of the autoclave process. The usage information may include a count of autoclave processes and durations of time periods between autoclave processes. The usage information may be used to determine times at which autoclave processes are performed.

Abstract: A first wireless device (WD) is installed at a known position, and a second WD is attached to a target of a sterilization process. A reading apparatus attempts reading identification information from WDs, and measures a relative amount of movement from a reference position using a self-localization technique. An estimation unit of a system estimates a position of the target based on the relative amount of movement of the reading apparatus from a time point when the first identification information has been read from the first WD to a time point when the second identification information has been read from the second WD. A database stores position information representing an estimated position of the target and sterilization-related information. The estimated position of the target selected based on the sterilization-related information is notified to a user based on the position information.

Abstract: An embodiment includes a wound dressing comprising: a shape memory polymer (SMP) foam, including open cells, having first and second states; and a hydrogel (HG) included within the cells; wherein (a) in a first position a composite, including the SMP foam and the HG, is configured to be located proximate a hemorrhagic tissue with the SMP foam in the first state; (b) in a second position the composite is configured to be expanded to the second state against the hemorrhagic tissue when the SMP foam is plasticized at 37° C. depressing a glass transition temperature (Tg) of the SMP foam to below 25° C. Other embodiments are described herein.

Abstract: A shingles remediation belt device is provided which may utilize a protective layer having a outer side surface and a inner side surface opposite the outer side surface, an absorptive layer having a outer side surface and a inner side surface opposite the outer side surface, a porous barrier layer having a outer side surface and a inner side surface opposite the outer side surface, and a sanitary layer having an outer side surface and an inner side surface opposite the outer side surface. Further, the inner side surface of the protective layer may be disposed adjacent the outer side surface of the absorptive layer, the inner side surface of the absorptive layer may be disposed adjacent the outer side surface of the porous barrier layer, and the inner side surface of the porous barrier layer may be disposed adjacent the outer side surface of the sanitary layer.

Abstract: A multi-layered scaffold useful for osteochondral complex defects. The multi-layered scaffold can be prepared by photopolymerizing a multi-layer scaffold precursor including: a first layer disposed on a surface of a second layer, wherein the first layer includes a first tri-block poly(lactide-co-propylene glycol-co-lactide) dimethacrylate; and the second layer includes a second tri-block poly(lactide-co-propylene glycol-co-lactide) dimethacrylate, hydroxyapatite nanoparticles covalently conjugated to one or more hydroxyethyl methacrylate moieties via an optional linker, and a photoinitiator, wherein the nanoparticles comprise hydroxyapatite, tricalcium phosphate, silicon dioxide, bioglass, or a mixture thereof.

Abstract: The present invention concerns a bio-adhesive comprising one or more protein-based polymers with catechol and quinone functionality wherein the polymer is substituted with at least 2 different functionalization agents each having a 3,4-dihydroxyphenyl group and each having a different resistance to oxidation, wherein the at least 2 different functionalization agents are oxidized to a different degree, wherein—the protein-based polymer is selected from silk, fibrin, collagen and/or gelatin, making up at least 50% by weight on the entire polymer content of the bio-adhesive, and—the ratio of the functionalization agents and amount of oxidant are selected such as to achieve a conversion of 4 to 96% of the catechol moieties into quinone moieties. It further concerns a bio-adhesive for application on the outside or inside of a living human or animal body, suitably, this may be in the form of a kit of parts.

Abstract: The invention relates to a calcified tissue substitute and methods of manufacturing and use related thereto. The methods for manufacturing a calcified tissue substitute include reacting ground nacre, monocalcium phosphate, and water to produce brushite; grinding the brushite; reacting ground nacre with the ground brushite disodium hydrogen phosphate solution. Methods for repairing and/or strengthening a calcified tissue in need thereof are provided, as well as a delivery device for delivering the calcified tissue substitute.

Abstract: An implantable scaffold device comprises a non-biodegradable backbone and a biodegradable dermal compartment comprising live cells. Method of fabricating implantable devices via 3D printing using a synthetic ink formulation coprinted with a biodegradable bioink.

Abstract: Elongated, curled cartilage fibers and shaped implants comprising them are disclosed, as well as methods for making and using them. A cohesive mass of intertwined cartilage fibers may be shaped to provide a shaped implant which conforms to an implant site. The implant may also be reshaped to have a second shape which conforms to an implant site. The implant site may be the cavity of a cartilage defect, or a space or pocket at a treatment site, any of which may have resulted from treatment, injury, or disease. The implant may be shaped or reshaped to conform to, or replace, an anatomical feature or portion thereof, for repair or treatment of the anatomical feature. Shaped implants comprising the cartilage fibers have good shape retention and are capable of completely filling, and resisting migration from, an implant site after administration and hydration.

Abstract: The present invention provides a tissue graft product comprising a plurality of laminated layers of extracellular matrix. wherein the extracellular matrix is derived from an amniotic membrane, and wherein the stromal side of an extracellular matrix layer is presented on both the upper and lower surfaces of the tissue graft product. Methods of making and using the tissue graft product also are provided.

Abstract: Novel process for decellularization of bovine bone graft for reconstruction of bone defects.

Abstract: The present invention relates to bioengineered collagen constructs and methods for the preparation and use of said constructs. The constructs and methods may find application in, but are not limited to, the provision of replacement tissue and/or cells, and/or the delivery of agents to biological targets such as tissues and cells. The constructs and methods may also find application in, but are not limited to, replacing endothelial tissue.

Abstract: The invention provides methods and polymer compositions for treating retinal detachment and other ocular disorders, where the methods employ polymer compositions that can form a hydrogel in the eye of a subject. The hydrogel is formed by reaction of (i) a nucleo-functional polymer that is a biocompatible polymer containing a plurality of thio-functional groups —R1-SH wherein R1 is an ester-containing linker, such as a thiolated poly(vinyl alcohol) polymer and (ii) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups.

Abstract: The present invention provides improved drug-eluting tube devices. In some embodiments, the tube devices deliver analgesics directly at sites of internal discomfort, including, but not limited to, internal membranes and implant entry sites. In some embodiments, the tube devices can be reloaded with drug in situ. In some embodiments, the tube devices comprise lubricating coatings to reduce painful friction with internal membranes. In some embodiments, the tube devices further include flexible and pliable regions that dampen force transmission to implanted sites, such as by inadvertent pulling.

Abstract: A surgical system including an implantable medical device having a size and shape. The surgical device having a substrate and a coating that covers at least a portion of the substrate. The coating including collagen, glycerin and a hemostatic agent. The substrate including a first piece and a second piece that is joined with the first piece. The first piece and the second piece forming a pocket having a cavity and an opening that is in communication with the cavity. The device being pre-formed such that a size and shape of the cavity conforms to the size and shape of the implantable medical device.