Developing high-efficiency base editors by combining optimized synergistic core components with new types of nuclear localization signal peptide

The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base editor(ABE) allow generating precise and irreversible base mutations in a programmable manner and have been used in many different types of cells and organisms. However, their applications are limited by low editing efficiency at certain genomic target sites or at specific target cytosine(C) or adenine(A) residues. Using a strategy of combining optimized synergistic core components, we developed a new multiplex super-assembled ABE(sABE) in rice that showed higher base-editing efficiency than previously developed ABEs. We also designed a new type of nuclear localization signal(NLS) comprising a FLAG epitope tag with four copies of a codon-optimized NLS(F4NLS^(r2)) to generate another ABE named F4NLS-sABE. This new NLS increased editing efficiency or edited additional A at several target sites. A new multiplex super-assembled CBE(sCBE) and F4NLS^(r2) involved F4NLS-sCBE were also created using the same strategy. F4NLS-sCBE was proven to be much more efficient than sCBE in rice. These optimized base editors will serve as powerful genome-editing tools for basic research or molecular breeding in rice and will provide a reference for the development of superior editing tools for other plants or animals.

On the Accordance of Religious and Scientific Cognition Mechanism

There are various differences and contraries, sometimes, even a vehement collision between religion and science. However, to the understanding of objective things, the cognition principles which the two follow are almost unanimous. Basically, mature religions have established complete theology systems, which are one of the means of human cognition, considering objective reality as cognitive basis, following cognitive universal rules and full of rationality and Irrationality through the cognitive process as well as science.

中国重要农业文化遗产的空间分布特征及其差异性管理策略

Climate change and rapid urbanization pose significant challenges to the conservation and management of agricultural heritage systems,including decline in agricultural land,loss of labor,and ecosystem degradation.Although existing studies have proposed general strategies with theoretical guidance and specific strategies for particular systems to promote the conservation of agricultural heritage systems,there remains a large knowledge gap in effective and differentiated management strategies at the regional level.This is especially so in China because of the clear regional differences in the natural and socioeconomic conditions of the widely distributed China Nationally Important Agricultural Heritage Systems(China-NIAHS).In this study,we integrated multi-source data and spatial analysis to reveal the distribution characteristics of existing China-NIAHS and proposed differentiated management strategies.Results show that there are four clustering distribution zones of China-NIAHS,i.e.,the northwest clustering zone west of the Heihe-Tengchong Line(ZoneⅠ),the clustering belt with‘Northeast-Hebei-Shandong'as core(ZoneⅡ),the Yangtze River Delta clustering zone(ZoneⅢ),and the Hunan-Chongqing-Yunnan-Guizhou clustering zone(ZoneⅣ).Different management strategies are proposed for the China-NIAHS in each clustering zone.Specifically,ZoneⅠshould focus on maintaining their ecological functions and services,while ZoneⅡshould aim for livelihood supply,sustainable resource use,and ecological protection.For ZoneⅢ,rapid urbanization could become a positive driving force for China-NIAHS conservation through sustainable tourism and reasonable urban zoning.ZoneⅣshould emphasize the mutual support between characteristic product development and the brand effect of the China-NIAHS.These findings will help establish regional and targeted management strategies for China-NIAHS and provide a reference for the conservation of agricultural heritage systems in other countries.