The present invention provides a half-life extension drug and a library thereof, and a preparation method and application thereof. Specifically, the present invention provides a drug library, comprising: (a) a drug unit; and (b) n half-life extension units, wherein the drug unit comprises a drug element portion and a first nucleic acid element portion connected to the drug element portion, and each half-life extension unit comprises a half-life extension element portion and a second nucleic acid element portion connected to the half-life extension element portion. Moreover, one first nucleic acid element portion of the drug unit and the second nucleic acid element portion of the at least one half-life extension unit may form a “drug unit-half-life extension unit” complex by forming a complementary base pairing structure, and n is a positive integer greater than or equal to 1.

The present disclosure relates to novel RNAi agents designed to decrease the expression of ANGPTL8 in the liver, where the RNAi agents comprise delivery moieties conjugated to oligonucleotides optionally via a linker. The RNAi agents are useful in the treatment of diseases involving the regulation of ANGPTL8 expression.

Disclosed herein are compounds according to Formula (I) comprising PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double stranded RNAi agents, to certain cell types, such for example skeletal muscle cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.

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Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

The disclosure provides modified biotin-binding proteins which can be expressed in soluble form in high yield in bacteria. Also provided are fusion proteins comprising the modified biotin-binding protein and an antigen. The disclosure further provides non-hemolytic variants of alpha-hemolysin from S. aureus and fusion protein comprising non-hemolytic variant of alpha-hemolysin and a biotin-binding domains. Immunogenic compositions comprising the proteins are also disclosed and use of such immunogenic compositions for inducing an immune response or for vaccinating a subject are also disclosed.

A camptothecin drug having a highly stable hydrophilic connecting unit and its conjugate, or its pharmaceutically acceptable salt thereof, including methods for preparation thereof, and its applications in preventing and/or treating cancer. The conjugate can specifically bind to receptors highly expressed in tumor cells. The conjugates have excellent water solubility, stability, and homogeneity, and can be used for preventing and/or treating tumors and/or other diseases.

Disclosed are bispecific compounds (degraders) that target α-synuclein protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat neurodegenerative diseases.

The design, synthesis, and biological evaluation of a new family of highly effective conjugate compounds, including dendrimeric moieties and branched structures, are described. Pharmaceutical compositions including the subject dendrimeric conjugates and methods of using the same are also provided. Methods of using the subject dendrimeric conjugates include delivering a cargo moiety conjugated to the dendrimeric moieties and branched structures to a cell under suitable conditions. In certain embodiments, the cell is a bacterial cell population, and the subject compounds reduce the bacterial cell population. In certain embodiments of the methods, the subject compound is capable of eradicating one or more of Gram-positive bacteria, mycobacteria, and Gram-negative bacteria. In certain embodiments of the methods, the subject compound is capable of eradicating bacterial biofilms. Methods of using the subject dendrimeric conjugates include treating a subject for a disease or condition. In certain embodiments, the disease or conditions an infectious disease.

Provided herein according to some embodiments of the invention are aryl boronate and/or aryl diaminoboryl compounds. Also provided are methods of detecting the presence of hydrogen peroxide (H.sub.2O.sub.2) and/or other reactive oxygen species (ROS) in a cell and/or tissue by contacting the cell and/or tissue with aryl boronate and/or aryl diaminoboryl compounds. Also provided according to embodiments of the invention are methods of producing persulfides in the presence of hydrogen peroxide (H.sub.2O.sub.2) and/or other reactive oxygen species (ROS) in a cell and/or tissue by contacting the cell and/or tissue with aryl boronate and/or aryl diaminoboryl compounds.

Disclosed are bispecific compounds (degraders) that target ITK or a zinc finger (ZnF) protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by ITK or ZnF protein activity.