Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13 has drawn broad interest to control gene expression and cell fate at the RNA level in general. Apart from RNA interference mediated by its endonuclease activity, the nuclease-deactivated form of Cas13 further provides a versatile RNA-guided RNA-targeting platform for manipulating kinds of RNA modifications post-transcriptionally. Chemical modifications modulate various aspects of RNA fate, including translation efficiency, alternative splicing, RNA–protein affinity, RNA–RNA interaction, RNA stability and RNA translocation, which ultimately orchestrate cellular biologic activities. This review summarizes the history of the CRISPR-Cas13 system, fundamental components of RNA modifications and the related physiological and pathological functions. We focus on the development of epi-transcriptional editing toolkits based on catalytically inactive Cas13, including RNA Editing for Programmable A to I Replacement (REPAIR) and xABE (adenosine base editor) for adenosine deamination, RNA Editing for Specific C-to-U Exchange (RESCUE) and xCBE (cytidine base editor) for cytidine deamination and dm6ACRISPR, as well as the targeted RNA methylation (TRM) and photoactivatable RNA m6A editing system using CRISPR-dCas13 (PAMEC) for m6A editing. We further highlight the emerging applications of these useful toolkits in cell biology, disease and imaging. Finally, we discuss the potential limitations, such as off-target editing, low editing efficiency and limitation for AAV delivery, and provide possible optimization strategies.
Copycat brands mimic brand leaders to free ride on the latter's equity. However, little is known regarding if and how consumers confuse copycat as leading brand in purchasing. In this study, we applied a word-pair evaluation paradigm in which the first word was a brand name (copycat vs. normal brand both similar with a leading brand in category), followed by a product name (near vs. far from the leading brand’s category). Behavioral results showed that, when the product is near the leader’s category, the copycat strategy (CN) was more preferred compared to the normal brand (NN) but not different in the far product condition (CF and NF). Event-related potential (ERP) data provided further insight into the mechanism. The N400 amplitude elicited by the CN condition was significantly smaller than NN. However, when products are far from the leader’s category, there was no significant difference in N400 amplitudes. For the late positive component (LPC), the CN gave rise to a larger amplitude than the CF. The N400 amplitude was suggested to reflect the categorization process, and the LPC demonstrated the recollection process in long-term memory. These findings imply that the copycat brand strategy is generally only effective when products are within the category of the leading brand, which offers important implications for marketing practices.
BackgroundSocial support is associated with cognitive function at an older age, but how distinct dimensions of social support affect trajectories of cognitive decline in older Chinese adults remains unclear.MethodsUsing longitudinal data (waves 1–4) from the China Health and Retirement Longitudinal Study, 7-year trajectories of cognitive decline by various social support markers, including family support, financial support, public support and perceived support, were estimated using latent growth curve modelling for adults aged 60 and over (N=6795).ResultsAfter adjusting for baseline sociodemographics, behaviours, body mass index and health conditions, all social support markers were associated with baseline cognitive function, except for living with spouse. Participants living with spouse experienced a slower cognitive decline (0.069 per year, 95% CI 0.006, 0.133) than those who were not. A faster cognitive decline was associated with co-residing with children (−0.053 per year, 95% CI −0.104, –0.003), receiving ≥¥5000 from children (−0.095 per year, 95% CI −0.179, –0.011), receiving financial support from others (−0.108 per year, 95% CI −0.208, –0.008) and perceived support (−0.068 per year, 95% CI −0.123, –0.013). When all markers were mutually adjusted for, the associations of living with spouse and receiving financial support from others with cognitive decline disappeared. Stratifying by rural–urban residence, medical insurance and meeting children 1–3 times per month were associated with a slower rate of cognitive decline in urban residents but not in rural residents.ConclusionOverall, our findings confirm that the effects of distinct domains of social support on cognitive decline vary. More equally good social security systems should be established in urban and rural China.
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