The therapeutic potential of phosphodiesterase 9 (PDE9) inhibitors: a patent review (2018-present).

INTRODUCTION: Phosphodiesterase 9 (PDE9) has been demonstrated as a potential target for neurological disorders and cardiovascular diseases, such as Alzheimer's disease and heart failure. For the last few years, a series of PDE9 inhibitors with structural diversities have been developed and patented by researchers and pharmaceutical companies, providing insights into first-in-class therapies of PDE9 drug candidates. AREA COVERED: This review provides an overview of PDE9 inhibitors in patents from 2018 to the present. EXPERT OPINION: Only a few of the current PDE9 inhibitors are highly selective over other PDEs, which limits their application in pharmacological and clinical research. The design and development of highly selective PDE9 inhibitors remain the top priority in future research. The advantages of targeting PDE9 rather than other PDEs in treating neurodegenerative diseases need to be explained thoroughly. Besides, application of PDE9 inhibitor-based combination therapies sheds light on treating diabetes and refractory heart diseases. Finally, PDE9 inhibitors should be further explored in clinical indications beyond neurological disorders and cardiovascular diseases.

Fast annealing fabrication of porous CuWO4photoanode for charge transport in photoelectrochemical water oxidation.

Ternary-phase CuWO4oxide with an electronic band gap of 2.2-2.4 eV is a potential candidate photoanode material for photoelectrochemical (PEC) water splitting. Herein, we present an efficient method to prepare CuWO4film photoanode by combining hydrothermal method and hybrid microwave annealing (HMA) process. In comparison with conventional thermal annealing (CTA), HMA can achieve CuWO4thin film within minutes by using SiC susceptor. When the CuWO4photoanode is prepared by HMA, its PEC water oxidation performance improves from 0.21 to 0.29 mA cm-2at 1.23 VRHEcomparing with the one prepared by CTA. The origin of the enhanced photocurrent was investigated by means of complementary physical characterizations and PEC methods. The results demonstrated that the obtained HMA processed CuWO4photoanode not only exhibited intrinsic porous nanostructures but also abundant surface hydroxyl groups, which facilitated sufficient mass transport and the charge transfer. Our results highlight the application of HMA for the fast fabrication of porous film photo-electrodes without using sacrificial template.

Complete genome sequence of a novel totivirus isolated from the leaves of Myrica rubra.

Chinese bayberry is a fruit that is appreciated for its taste. A novel totivirus associated with rolling, disfiguring, chlorotic and vein-clearing symptoms on the leaf apices of Chinese bayberry was identified by transcriptome sequencing and reverse transcription PCR (RT-PCR). The complete genome of the virus was determined to be 4959 nucleotides long, and it contains two open reading frames (ORFs). Its genomic organization is similar to that of previously reported totiviruses. ORF1 encodes a putative coat protein (CP) of 765 aa, and ORF2 encodes an RNA-dependent RNA polymerase (RdRp) of 815 aa. These two putative proteins share 55.1% and 62.6%, amino acid sequence identity, respectively, with the corresponding proteins of Panax notoginseng virus A, respectively. According to the demarcation criteria for totivirus species established by the International Committee on Taxonomy of Viruses (ICTV), the new virus should be considered a member of a new species in the genus totivirus, family Orthototiviridae, which we have tentatively named ''Myrica rubra-associated totivirus'' (MRaTV).