Abstract: A high aspect ratio in-plane metal microneedle array, a manufacturing method and a clamping and inserting auxiliary device thereof is disclosed. A large-size metal sheet is cut into small metal sheets. A clamping tooling composed of two upper and lower metal cover plates is processed. Inner sides of the upper and the lower cover plates of the tooling are provided with grooves in which the metal sheets are placed and fastened by bolts. Wire cutting is conducted on the tooling and the metal sheets as a whole to obtain a plane metal microneedle array with a plurality of microneedle bodies. In addition, an assembling and clamping device and an inserting auxiliary device of the high aspect ratio in-plane metal microneedle array is provided. The assembled inserting auxiliary device is placed on skin, and the microneedle array is inserted into the skin through the auxiliary device.

Abstract: Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.

Abstract: Provided is a genetically modified microorganism for the production of a derivative of 4-hydroxy-2-ketobutyrate selected in the group consisting of 1,3-propanediol, 3-hydroxypropionaldehyde, 3-hydroxypropionate and 2,4-dihydroxybutyrate, the microorganism further having a gene coding for a mutant phosphoserine aminotransferase having an improved L-homoserine aminotransferase activity converting by transamination L-homoserine into 4-hydroxy-2-ketobutyrate. Also provided is a method for the production of derivatives of 4-hydroxy-2-ketobutyrate selected in the group consisting of 1,3-propanediol, 3-hydroxypropionaldehyde, 3-hydroxypropionate and 2,4-dihydroxybutyrate by culturing the genetically modified microorganism in a culture medium and recovering the desired derivative.

Abstract: The present invention concerns a genetically modified microorganism for the production of a derivative of 4-hydroxy-2-ketobutyrate selected in the group consisting of 1,3-propanediol, 3-hydroxypropionaldehyde, 3-hydroxypropionate and 2,4-dihydroxybutyrate, said microorganism further comprising a gene coding for a mutant phosphoserine aminotransferase having an improved L-homoserine aminotransferase activity converting by transamination L-homoserine into 4-hydroxy-2-ketobutyrate. The invention also concerns a method for the production of derivatives of 4-hydroxy-2-ketobutyrate selected in the group consisting of 1,3-propanediol, 3-hydroxypropionaldehyde, 3-hydroxypropionate and 2,4-dihydroxybutyrate by culturing said genetically modified microorganism in a culture medium and recovering the desired derivative.