Abstract: Methods are disclosed herein for producing human hepatocytes from human induced pluripotent stem cells. Also provided are transgenic rats for the expansion of human hepatocytes, such as those produced using the methods disclosed herein.

Abstract: The present disclosure relates to the engraftment and proliferation of cells in fat-associated lymphoid clusters (“FALCs” or “milky spots”), which may be used to generate functional ectopic tissue. The present disclosure further provides methods and compositions for grafting and proliferating cells, in FALCs by activating the lymphotoxin beta receptor (LT?R) and/or NF-?B-inducing kinase (NIK) signaling pathway. The present disclosure also provides for methods and compositions to establish ectopic liver tissue in FALCs (milky spots) and to use such ectopic liver tissue for therapeutic benefit, and provides methods and compositions to generate ectopic kidney tissue in FALCs, which can be used in a subject for therapeutic benefit.

Abstract: The present invention relates to methods of treating infectious, inflammatory and post-traumatic disorders by administering various compounds newly discovered to have TLR4 inhibitory activity. In addition to methods of treatment, the present invention further provides for pharmaceutical compositions comprising said compounds, together with a suitable pharmaceutical carrier. Because TLR4 is the most upstream receptor in the pro-inflammatory LPS signaling cascade, treatments of the invention, which inhibit or antagonize TLR4 action, may avoid the pitfalls associated with other cytokine inhibitors that act further down the pathway and accordingly play a less specific (and perhaps non-critical) role.

Abstract: The present disclosure concerns embodiments of an implantable perfusion device that can be implanted in an injured blood vessel to control bleeding without occluding the vessel. In one specific implementation, the perfusion device can be implanted percutaneously into a patient's descending aorta to control bleeding at the site of a ruptured portion of the aorta (known as torso hemorrhage) while still allowing for the antegrade flow of blood from a location upstream of the ruptured portion of the aorta to a location downstream of the ruptured portion of the aorta. The perfusion device can be left inside the patient as the patient is transported to a medical facility where the injury can be repaired. Following repair of the vessel, the perfusion device can be withdrawn from the patient.

Abstract: Antisense oligonucleotides (ASOs) that disrupt RNA-RNA interactions of influenza virus genome segments that are required for virus packaging are described. The ASOs can be used to inhibit influenza A virus replication in vitro and in vivo. Use of the ASOs for the treatment of a subject with an influenza virus infection is also described.

Abstract: Novel compounds are disclosed along with methods of inhibiting the TGF? pathway and methods of treating Idiopathic Pulmonary Fibrosis (IPF) using such compounds.

Abstract: Recombinant transforming growth factor (TGF)-? monomers modified to inhibit dimerization and block TGF-? signaling are described. The recombinant TGF-? monomers lack the ability to bind and recruit TGF-? type I receptor (T?R1), but retain the capacity to bind the high affinity TGF-? type II receptor (T?RII), and in some instances, include mutations that increase their affinity for T?RII. Nucleic acid molecules and vectors encoding the recombinant TGF-? monomers are also described. Isolated cells, such as T cells, can be re-programmed with a TGF-? monomer-encoding nucleic acid or vector to secrete the monomer. Use of the recombinant TGF-? monomers and/or cells producing the recombinant TGF-? monomers, to inhibit TGF-? signaling, such as to treat disorders associated with aberrant TGF-? signaling, are also described.

Abstract: The present invention relates to methods and compositions for determining whether a subject having prostate cancer is at greater risk of developing progressive disease, and methods of treating the subjects. It is based, at least in part, on the discovery that approximately 90% of men carrying at least one of the following fusion genes: TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67 and CCNH-C5orf30 experienced prostate cancer recurrence, metastases and/or prostate cancer-specific death after radical prostatectomy (each examples of “progressive prostate cancer”), while these outcomes occurred in only 36% of men not carrying any of these fusion genes. It is also based, at least in part, on the discovery that no patient studied survived five years without recurrence if their primary prostate cancer contained a TRMT11-GRIK2 or MTOR-TP53BP1 fusion gene. It is also based, at least in part, on the discovery that the protein encoded by the MAN2A1-FER fusion gene exhibits kinase activity.

Abstract: Compounds, pharmaceutical compositions, and methods for reversing fosfomycin resistance are disclosed. Embodiments of the disclosed compounds inhibit fosfomycin-inhibiting enzymes. Some embodiments of the compounds are FosA inhibitors. The disclosed pharmaceutical compositions include (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) a compound, or a pharmaceutically acceptable salt thereof, which inhibits a fosfomycin-inhibiting enzyme. A method of inhibiting growth of a fosfomycin-resistant bacterium includes contacting the bacterium with (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof.

Abstract: The presently disclosed subject matter is directed to dual specificity mitogen-activated protein kinase phosphatase (DUSP-MKP) inhibitors that sensitize cancer cells immune cell killing and methods of using the disclosed DUSP-MKP inhibitors for the treatment of cancer.

Abstract: The present disclosure provides recombinant T cells that include a vector encoding one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1?), mitochondrial transcription factor A (Tfam), GA binding protein transcription factor alpha subunit (GABPA), and estrogen-related receptor alpha (ERR? ). Such recombinant T cells can also include a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). Methods of using these recombinant T cells in cancer immunotherapy are provided. Also provided are kits and compositions that can be used with such methods.

Abstract: This application provides methods of treating Krabbe disease, for example in an infant. Such methods can include immunosuppressing the patient, for example by administration of a myeloablative regimen, administering an umbilical cord blood transplant (UCBT) (such as an allogenic UCBT), and increasing expression of galactocerebrosidase (GALC) in the patient (e.g., by using gene editing).

Abstract: Disclosed herein are novel amine-functionalized porphyrin compounds, as wells as pharmaceutically acceptable salts or esters thereof. The disclosed compounds can be used to impart antioxidant, anti-inflammatory, anti-microbial, and/or cell-adhesion specificity to a surface or material in need thereof, such as a surface of an indwelling medical implant, or a marine surface.

Abstract: Methods are disclosed for inhibiting the development of a tumor in a subject. The methods include administering to a subject a therapeutically effective amount of a dominant negative tumor necrosis factor (DN-TNF)-? protein and/or a nucleic acid encoding the DN-TNF-? protein. The DN-TNF-? protein and/or a nucleic acid encoding the DN-TNF-? protein can be administered alone or in combination with other agents.

Abstract: The present invention relates to tolerogenic mammalian dendritic cells (iDCs) and methods for the production of tolerogenic DCs. In addition, the present invention provides methods for administration of tolerogenic dendritic cells as well as particles containing oligonucleotides to mammalian subjects. Enhanced tolerogenicity in a host can be useful for treating inflammatory and autoimmune related diseases, such as type 1 diabetes.

Abstract: The invention relates to ex-situ biosensors that impedimetrically detect one or more target biomarkers of interest in bodily fluid sample derived from a patient. The biosensors include a multi-array of conducting material, such as platinum wires, having immobilized thereon antibody and/or aptamer that is selected to specifically and selectively bind to the one or more target biomarkers of interest. The biosensors are contacted with a portion of the bodily fluid sample, and the antibody and/or aptamer binds to the target biomarker(s) of interest in the bodily fluid sample. As a result, an electrochemical impedance signal is generated and therefore, a change in the electrochemical impedance is indicative of the presence of the target biomarker(s) of interest in the bodily fluid sample. The biosensors are point-of-care, on-demand devices that can be used in a medical environment, as well as in domestic and health emergency settings.

Abstract: A digital microfluidic system includes a substrate, a plurality of electrode sets provided on the substrate, wherein each of the electrode sets includes two co-planar interdigitated finger electrodes, and a driving circuit including an AC/DC voltage source and a controller. Each of the electrode sets is individually addressable by the driving circuit under control of the controller such that an AC/DC voltage generated by the AC/DC voltage source may be selectively provided to one or more of the electrode sets. Also, an anti-biofouling electrode for a digital microfluidic system includes an electrode layer, and a slippery liquid infused porous surface structure provided on the electrode layer.

Abstract: The present invention relates to compositions including nano-particles and a nano-structured support matrix, methods of their preparation and applications thereof. The compositions of the present invention are particularly suitable for use as anode material for lithium-ion rechargeable batteries. The nano-structured support matrix can include nanotubes, nanowires, nanorods, and mixtures thereof. The composition can further include a substrate on which the nano-structured support matrix is formed. The substrate can include a current collector material.

Abstract: The present invention relates to compositions and methods for targeted administration to the pancreas of a calcineurin inhibitor and a non-steroidal anti-inflammatory drug (“NSAID”) to reduce the risk and/or limit the extent of post-imaging pancreatitis associated with procedures that employ a radiocontrast medium, particularly procedures that selectively image the pancreas, gallbladder and/or biliary tree.

Abstract: A method comprising: introducing a sample volume into an inlet end of a liquid chromatography column, wherein the liquid chromatography column includes a focusing segment proximal to the inlet end of the liquid chromatography column and a separation segment proximal to an elute outlet of the liquid chromatography column; maintaining only the focusing segment at a first temperature as the sample is introduced into the focusing segment; and subsequently heating the focusing segment to a second temperature that is higher than the first temperature after the entire sample volume has been introduced into the focusing segment.