Abstract: Disclosed herein are compositions, methods, kits, and systems relating to efficient delivery of cargos (e.g., therapeutic cargos) into cells, for instance, for in vivo delivery. The present disclosure provides lipid-containing particles (e.g., virus-like particles) for delivering therapeutic cargos. The present disclosure also provides polynucleotides encoding the lipid-containing particles provided herein, which may be useful for producing said lipid-containing particles. Also provided are methods for editing nucleic acid molecules in cells using the lipid-containing particles provided herein, as well as cells and kits comprising the lipid-containing particles.

Abstract: Disclosed herein are compositions, methods, kits, and systems relating to efficient delivery of cargos (e.g., therapeutic cargos) into cells, for instance, for in vivo delivery. The present disclosure provides lipid-containing particles (e.g., virus-like particles) for delivering therapeutic cargos. The present disclosure also provides polynucleotides encoding the lipid-containing particles provided herein, which may be useful for producing said lipid-containing particles. Also provided are methods for editing nucleic acid molecules in cells using the lipid-containing particles provided herein, as well as cells and kits comprising the lipid-containing particles.

Abstract: An optical metasurface film includes a flexible polymeric film having a first major surface, a patterned polymer layer having a first surface proximate to the first major surface of the flexible polymeric film and having a second nanostructured surface opposite the first surface, and a refractive index contrast layer adjacent to the nanostructured surface of the patterned polymer layer forming a nanostructured bilayer with a nanostructured interface. The nanostructured bilayer acts locally on amplitude, phase, or polarization of light, or a combination thereof and imparts a light phase shift that varies as a function of position of the nano structured bilayer on the flexible polymeric film. The light phase shift of the nanostructured bilayer defines a predetermined operative phase profile of the optical metasurface film.

Abstract: This invention relates to compounds that may be useful as inhibitors of Mitogen-activated Protein Kinase Kinase Kinase Kinase-4 (MAP4K4). The invention also relates to the use these compounds, for example in a method of treatment of cardiac conditions.

Abstract: The present invention generally relates, in some aspects, to articles and methods relating to nanosensors for determination of molecules and other features, e.g., via surface plasmonic resonance, electric resonance, magnetic resonance, color changes, or the like. These articles and methods may be used, for example, for sample detection. The articles described in some aspects of the invention include a microwell array and a nanosensor array. In some embodiments, The nanosensor arrays may utilize nanoparticles positioned on nanostructures that are able to interact with a sample suspected of containing an analyte, such as a single cell. The interaction between nanoparticles and a sample can be detected by a change in applied energy, such as altered electromagnetic radiation caused by surface plasmonic resonance of incident visible light, and/or other types of resonance.

Abstract: Embodiments of the present disclosure concern the treatment and/or prevention of eye disorders, including dry eye disorders and any medical condition that has dry eye as a symptom. In specific embodiments, treatment and/or prevention may occur by administering therapeutic compositions comprising one or more RXR agonists to at least one eye of an individual.

Abstract: An upper limb rehabilitation device for sarcopenia and its application method are provided, which is less likely to cause harm to patients, more suitable for people with weaker strength, can encourage to exercise combined with fun, and can significantly improve the upper limb muscle function of sarcopenia patients. The upper limb rehabilitation device for sarcopenia includes an outer surface, a filling material, and a keel. The shape of the outer surface is shuttle shaped, the keel is made of rubber material, the filling material is between the keel and the outer surface, including sponge particles and wormwood particles, and hand acupoint protrusion particles are set on the outer surface.

Abstract: The present disclosure encompasses methods for generating cells or tissue from existing cells with one or more mutated variants of Yap. In specific embodiments, the disclosure regards treatment of existing cardiomyocytes with one or more mutated variants of Yap that causes them to divide and generate new cardiomyocytes. In specific cases, the mutated variant of Yap has serine-to-alanine substitutions at 1, 2, 3, 4, 5, 6, or more serines of Yap.

Abstract: A magnetic-field-adjustable micromagnetic orthodontic accelerator includes a cheek side plate, a tongue side plate and a supporting plate to form a structure of teeth sleeves, cheek side magnets and tongue side magnets are arranged on the cheek side plate and the tongue side plate respectively, the cheek side magnets and the tongue side magnets form a micro magnetic field environment around roots of to-be-moved teeth receiving orthodontic treatment, physiological magnetic field loss caused by traction of the orthodontic accessory is effectively compensated, metabolism and reconstruction of periodontal tissue of the to-be-moved teeth are promoted, and the orthodontic teeth moving process is accelerated.

Abstract: An upper limb rehabilitation device for sarcopenia and its application method are provided, which is less likely to cause harm to patients, more suitable for people with weaker strength, can encourage to exercise combined with fun, and can significantly improve the upper limb muscle function of sarcopenia patients. The upper limb rehabilitation device for sarcopenia includes an outer surface, a filling material, and a keel. The shape of the outer surface is shuttle shaped, the keel is made of rubber material, the filling material is between the keel and the outer surface, including sponge particles and wormwood particles, and hand acupoint protrusion particles are set on the outer surface.

Abstract: This invention provides a hand-held stereovision (HHS) system that is an efficient, accurate, and radiation-free imaging device to acquire intraoperative profiles of the exposed spine in prone position. The reconstructed intraoperative stereovision surfaces (iSV) are registered with preoperative CT (pCT; supine position) in a nonrigid fashion to generate updated CT images (uCT) and correct for vertebral posture and alignment changes. Updated CT images are uploaded to a commercial navigation system for surgical navigation.

Abstract: The present disclosure provides methods of treating lysosomal storage disorders, e.g., Fabry disease, Gaucher disease, Farber disease, and Pompe disease. The method comprises producing vector-transduced T-Rapa cells that express a transgene of interest and administering the cells to a patient in need thereof. The T-Rapa cells may be transduced with a dual promoter lentivirus vector.

Abstract: Systems, methods, network devices, and machine-readable media disclosed herein include encoding data for storage or transmission by encoding the data according to a tamper-resistant data encoding scheme that renders the data secure against unbounded polynomial size attacks. The present disclosure further includes subsequently determining whether the data has been tampered with, and notifying a processor when the data has been modified or compromised.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.

Abstract: Provided are single-domain antibodies (sdAbs), also called heavy-chain-only variable domains (VHHs) or camelids, that contain reactive, non-canonical amino acids (ncAAs) and crosslink to target antigen protein. The target antigen may be a toxin or a neurotoxin produced by a pathogenic organism or microorganism that causes or is associated with a disease or pathology. Compositions and methods using the reactive ncAA-containing sdAbs to treat subjects afflicted with a pathology caused by a toxin- or neurotoxin-producing pathogen, such as Botulinum, are provided. In some cases, the compositions and methods comprising the sdAbs treat or prevent intoxication and inhibit and/or neutralize toxin or neurotoxin activity.

Abstract: An electrochemical apparatus includes an array of pixels disposed on a chip, stimulator circuitry disposed on the chip and configured to provide electrical input signals to cause stimulation of the pixels of the array, and sensor circuitry disposed on the chip and configured to read electrical output signals from the pixels of the array. The stimulator circuitry is configured to provide the input signals to cause stimulation of the pixels individually, and the sensor circuitry is configured to selectively read the output signals from the pixels while the pixels are being stimulated. The sensor circuitry is configured to measure an open-circuit voltage at each of the pixels and a current flow at each of the pixels while the pixels are being stimulated by the stimulator circuitry. The open-circuit voltage may be measured while the current flow is being measured.

Abstract: Nucleic acid molecules, compositions, recombinant AAV (rAAV) particles, kits, and methods are described herein for delivering a base editor (or “nucleobase editor”) to cells, e.g., via AAV vectors. In particular, the disclosure provides compositions, methods, and uses for delivery of adenine base editors and cytosine base editors in a single AAV vector (or genome). Further described herein are improved AAV vectors containing size-minimized regulatory components that enable, e.g., the packaging of base editors. Provided herein are methods and compositions for delivering base editor proteins to a cell or tissue in a single recombinant AAV (rAAV) vector. Contemplated herein are improved methods and compositions for delivering these base editors in vivo, in a single rAAV particle. Further provided herein are base editors and compositions and cells comprising these base editors.

Abstract: Disclosed is biguanide derivative of ibuprofen represented by the formula I, wherein the compound of formula I is N-carbamimidoyl-2-(2-(4-sobutylphenyl) propanoyl) hydrazine-1-carboximidamide. The biguanide derivative of ibuprofen of the present invention helps in significant reduction glucose levels in patients with diabetics as compared patients taking only metformin or similar biguanide. Further, the biguanide derivative of ibuprofen provides synergistic effect in lowering blood glucose level along with reducing inflammation in lower doses as compared to doses taken separately.

Abstract: Embodiments of the disclosure concern the use of expression constructs in which at least one polyA signal is embedded upstream of an expressible transcript, such as within a 5? UTR for the transcript, for example. In certain embodiments, the polyA signal is comprised within a ligand-binding aptamer, and the binding of the ligand to the aptamer, or lack thereof, dictates the outcome for the expressible transcript. In specific embodiments, absence of the ligand causes the expressed transcript having a polyA in its 5? UTR to be expressed but then degraded, whereas presence of the ligand causes inhibition of degradation upon expression of the expressible transcript. More than one ligand-binding aptamer may be present on the same expression construct.

Abstract: The present disclosure provides virus-like particles (VLPs) for delivering prime editors, and systems comprising such prime editor (PE) VLPs. The present disclosure also provides polynucleotides encoding the PE-VLPs described herein, which may be useful for producing said PE-VLPs. Also provided herein are methods for editing the genome of a target cell by introducing the presently described PE-VLPs into the target cell. The present disclosure also provides fusion proteins that make up a component of the PE-VLPs described herein, as well as polynucleotides, vectors, cells, and kits.