Glycogen metabolism is a form of crucial metabolic reprogramming in cells. PYGB, the brain-type glycogen phosphorylase (GP), serves as the rate-limiting enzyme of glycogen catabolism. Evidence is mounting for the association of PYGB with diverse human diseases. This review covers the advancements in PYGB research across a range of diseases, including cancer, cardiovascular diseases, metabolic diseases, nervous system diseases, and other diseases, providing a succinct overview of how PYGB functions as a critical factor in both physiological and pathological processes. We present the latest progress in PYGB in the diagnosis and treatment of various diseases and discuss the current limitations and future prospects of this novel and promising target.

High-throughput genetic screening is useful for discovering critical genes or gene sequences that trigger specific cell functions and/or phenotypes. Loss-of-function genetic screening is mainly achieved through RNA interference (RNAi), CRISPR knock-out (CRISPRko), and CRISPR interference (CRISPRi) technologies. Gain-of-function genetic screening mainly depends on the overexpression of a cDNA library and CRISPR activation (CRISPRa). Base editing can perform both gain- and loss-of-function genetic screening. This review discusses genetic screening techniques based on Cas9 nuclease, including Cas9-mediated genome knock-out and dCas9-based gene activation and interference. We compare these methods with previous genetic screening techniques based on RNAi and cDNA library overexpression and propose future prospects and applications for CRISPR screening.

Rabbit haemorrhagic disease virus (RHDV), European brown hare syndrome virus (EBHSV), rabbit calicivirus (RCV), and hare calicivirus (HaCV) belong to the genus Lagovirus of the Caliciviridae family that causes severe diseases in rabbits and several hare (Lepus) species. Previously, Lagoviruses were classified into two genogroups, e.g., GI (RHDVs and RCVs) and GII (EBHSV and HaCV) based on partial genomes, e.g., VP60 coding sequences. Herein, we provide a robust phylogenetic classification of all the Lagovirus strains based on full-length genomes, grouping all the available 240 strains identified between 1988 and 2021 into four distinct clades, e.g., GI.1 (classical RHDV), GI.2 (RHDV2), HaCV/EBHSV, and RCV, where the GI.1 clade is further classified into four (GI.1a–d) and GI.2 into six sub-clades (GI.2a–f). Moreover, the phylogeographic analysis revealed that the EBHSV and HaCV strains share their ancestor with the GI.1, while the RCV shares with the GI.2. In addition, all 2020–2021 RHDV2 outbreak strains in the USA are connected to the strains from Canada and Germany, while RHDV strains isolated in Australia are connected with the USA-Germany haplotype RHDV strain. Furthermore, we identified six recombination events in the VP60, VP10, and RNA-dependent RNA polymerase (RdRp) coding regions using the full-length genomes. The amino acid variability analysis showed that the variability index exceeded the threshold of 1.00 in the ORF1-encoded polyprotein and ORF2-encoded VP10 protein, respectively, indicating significant amino acid drift with the emergence of new strains. The current study is an update of the phylogenetic and phylogeographic information of Lagoviruses that may be used to map the evolutionary history and provide hints for the genetic basis of their emergence and re-emergence.