Nowadays, high epidemic obesity-triggered hypertension and diabetes seriously damage social public health. There is now a general consensus that the body’s fat content exceeding a certain threshold can lead to obesity. Calcium ion is one of the most abundant ions in the human body. A large number of studies have shown that calcium signaling could play a major role in increasing energy consumption by enhancing the metabolism and the differentiation of adipocytes and reducing food intake through regulating neuronal excitability, thereby effectively decreasing the occurrence of obesity. In this paper, we review multiple calcium signaling pathways, including the IP3 (inositol 1,4,5-trisphosphate)-Ca2+ (calcium ion) pathway, the p38-MAPK (mitogen-activated protein kinase) pathway, and the calmodulin binding pathway, which are involved in biological clock, intestinal microbial activity, and nerve excitability to regulate food intake, metabolism, and differentiation of adipocytes in mammals, resulting in the improvement of obesity.

Cytosine or adenine base editors (CBEs or ABEs) hold great promise in therapeutic applications because they enable the precise conversion of targeted base changes without generating of double-strand breaks. However, both CBEs and ABEs induce substantial off-target DNA editing, and extensive off-target RNA single nucleotide variations in transfected cells. Therefore, the potential effects of deaminases induced by DNA base editors are of great importance for their clinical applicability. Here, the transcriptome-wide deaminase effects on gene expression and splicing is examined. Differentially expressed genes (DEGs) and differential alternative splicing (DAS) events, induced by base editors, are identified. Both CBEs and ABEs generated thousands of DEGs and hundreds of DAS events. For engineered CBEs or ABEs, base editor-induced variants had little effect on the elimination of DEGs and DAS events. Interestingly, more DEGs and DAS events are observed as a result of over expressions of cytosine and adenine deaminases. This study reveals a previously overlooked aspect of deaminase effects in transcriptome-wide gene expression and splicing, and underscores the need to fully characterize such effects of deaminase enzymes in base editor platforms.

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Prime editors (PEs) are promising genome editing tools, but efficiency pre-testing of prime editing guide RNA (pegRNA) design is still laborious and time-consuming due to the lack of accurate and universal approaches. Here, we design a customized attention-based model OPED and train it using transfer learning to improve the accuracy and universality of efficiency prediction and design optimal pegRNAs. We demonstrate its powerful generalization capability across diverse published test datasets. Furthermore, we extend OPED to design optimal pegRNAs and single guide RNAs (sgRNAs) to install various ClinVar human pathogenic variants, and 28 of 30 (93.33%) target sites yield desired variants with few byproducts and practical editing efficiencies of up to 29.30%, 82.84%, and 90.05% for PE2, PE3/PE3b, and ePE systems, respectively. We construct the OPEDVar database of optimal designs from over two billion candidates for all ClinVar variants and provide a user-friendly web application of OPED for any intended edit.