Abstract: Provided herein are agents and methods for selectively killing senescent cells that are associated with numerous pathologies and diseases, including age-related pathologies and diseases. As disclosed herein, senescent cell-associated diseases and disorders may be treated or prevented by administering at least one senolytic agent or pharmaceutical compositions thereof. The senescent cell-associated diseases or disorders treated or prevented by the agents and methods described herein include, but are not limited to, cardiovascular diseases or disorders, cardiovascular diseases and disorders associated with arteriosclerosis, such as atherosclerosis, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), osteoarthritis, inflammatory or autoimmune diseases or disorders, pulmonary diseases or disorders, neurological diseases or disorders, dermatological diseases or disorders, chemotherapeutic side effects, radiotherapy side effects, metastasis and metabolic diseases.

Abstract: Provided herein are combinations comprising a glucagon-like peptide-1 receptor (GLP-1R) agonist and a thyroid hormone receptor beta (THR?) agonist and methods comprising administering to a subject in need thereof such combinations.

Abstract: Provided herein are combinations for inhibiting tyrosine kinase activity of a protein selected from Abelson protein (ABL1), Abelson-related protein (ABL2), or a chimeric protein BCR-ABL1, compositions thereof, methods of inhibiting tyrosine kinase enzymatic activity of a protein selected from Abelson protein (ABL1), Abelson-related protein (ABL2), or a chimeric protein BCR-ABL1, and methods for treating diseases wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and/or symptomology of the disease.

Abstract: Provided herein are combinations comprising a glucagon-like peptide-1 receptor (GLP-1R) agonist and a thyroid hormone receptor beta (THR?) agonist and methods comprising administering to a subject in need thereof such combinations.

Abstract: Provided herein are agents and methods for selectively killing senescent cells that are associated with numerous pathologies and diseases, including age-related pathologies and diseases. As disclosed herein, senescent cell-associated diseases and disorders may be treated or prevented by administering at least one senolytic agent or pharmaceutical compositions thereof. The senescent cell-associated diseases or disorders treated or prevented by the agents and methods described herein include, but are not limited to, cardiovascular diseases or disorders, cardiovascular diseases and disorders associated with arteriosclerosis, such as atherosclerosis, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), osteoarthritis, inflammatory or autoimmune diseases or disorders, pulmonary diseases or disorders, neurological diseases or disorders, dermatological diseases or disorders, chemotherapeutic side effects, radiotherapy side effects, metastasis and metabolic diseases.

Abstract: Provided herein are agents and methods for selectively killing senescent cells that are associated with numerous pathologies and diseases, including age-related pathologies and diseases. As disclosed herein, senescent cell-associated diseases and disorders may be treated or prevented by administering at least one senolytic agent or pharmaceutical compositions thereof. The senescent cell-associated diseases or disorders treated or prevented by the agents and methods described herein include, but are not limited to, cardiovascular diseases or disorders, cardiovascular diseases and disorders associated with arteriosclerosis, such as atherosclerosis, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), osteoarthritis, inflammatory or autoimmune diseases or disorders, pulmonary diseases or disorders, neurological diseases or disorders, dermatological diseases or disorders, chemotherapeutic side effects, radiotherapy side effects, metastasis and metabolic diseases.

Abstract: A landing leg assembly for a heavy duty commercial vehicle includes a first leg member defining an interior space, a second leg member telescopingly engaging the first leg member and movable between a retracted position and an extended position with respect to the first leg member, a gear assembly at least partially located within the interior space of the first leg member and operably coupled to the second leg member and configured to receive an input from a user to move the first leg member between the retracted and extended positions, the gear assembly including a shaft member and a gear member fixed for rotation with the shaft member, and an integral, single-piece bearing member including a bore that rotatably receives the shaft member, wherein the bearing member comprises a powdered metal and is directly welded to the first leg member.

Abstract: A landing leg assembly for a heavy duty commercial vehicle includes a first leg member defining an interior space, a second leg member telescopingly engaging the first leg member and movable between a retracted position and an extended position with respect to the first leg member, a gear assembly at least partially located within the interior space of the first leg member and operably coupled to the second leg member and configured to receive an input from a user to move the first leg member between the retracted and extended positions, the gear assembly including a shaft member and a gear member fixed for rotation with the shaft member, and an integral, single-piece bearing member including a bore that rotatably receives the shaft member, wherein the bearing member comprises a powdered metal and is directly welded to the first leg member.

Abstract: Provided are compounds, compositions and methods for improving resistance to skeletal muscle fatigue comprising administering an effective amount of a skeletal muscle troponin activator. Also provided are methods for improving resistance to fatigue, improving physical endurance, or reducing exercise intolerance in a subject suffering from a condition associated with muscle fatigue or weakness, such as heart failure.

Abstract: Provided are compositions and methods for improving diaphragm function in a patient. In some embodiments, the methods comprise administering to a patient or contacting a diaphragm skeletal muscle fiber with an effective amount of a skeletal muscle troponin activator or pharmaceutically acceptable salt thereof. Likewise, compositions and methods are also provided for increasing the function, activity, efficiency, sensitivity to calcium, or time to fatigue of skeletal muscle in the diaphragm. In some embodiments, the patient receiving such administration suffers from diaphragmatic atrophy.

Abstract: Provided are compounds, compositions and methods for improving resistance to skeletal muscle fatigue comprising administering an effective amount of a skeletal muscle troponin activator. Also provided are methods for improving resistance to fatigue, improving physical endurance, or reducing exercise intolerance in a subject suffering from a condition associated with muscle fatigue or weakness, such as heart failure.

Abstract: Provided are compositions and methods for improving diaphragm function in a patient by administering to the patient an effective amount of a skeletal muscle troponin activator or a pharmaceutically acceptable salt thereof.