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The CRISPR/Cas9 system offers a powerful tool for gene editing to enhance rice productivity. In this study, we successfully edited eight RR-TZF genes in japonica rice Nipponbare using CRISPR-Cas9 technology, achieving a high editing efficiency of 73.8%. Sequencing revealed predominantly short insertions or deletions near the PAM sequence, along with multi-base deletions often flanked by identical bases. Off-target analysis identified 5 out of 31 predicted sites, suggesting the potential for off-target effects, which can be mitigated by designing gRNAs with more than three base mismatches. Notably, new mutations emerged in the progeny of several gene-edited mutants, indicating inheritable genetic mutagenicity. Phenotypic analysis of homozygous mutants revealed varied agronomic traits, even within the same gene, highlighting the complexity of gene-editing outcomes. These findings underscore the importance of backcrossing to minimize off-target and inheritable mutagenicity effects, ensuring more accurate trait evaluation. This study offers insights into CRISPR/Cas9 mechanisms and uncertain factors and may inform future strategies for rice improvement, prompting further research into CRISPR/Cas9's precision and long-term impacts. [ABSTRACT FROM AUTHOR]

In contemporary times, cancer poses the most significant threat to human life and safety. Scientists have relentlessly pursued the intricacies of carcinogenesis and explored ways to prevent and treat cancer. Carcinogenesis is a complex, multi-faceted, and multi-stage process, with numerous underlying causes, including inflammation and fibrosis. Cancer-associated fibroblasts (CAFs), however, occupy a pivotal and substantial role within the tumor microenvironment, facilitating carcinogenesis through diverse mechanisms such as creating inflammation, fostering a fibrotic tumor microenvironment, and immunosuppression. In this paper, we introduce the concept of carcinogenesis, explain its causes, describe the characteristics of CAFs and their sources, and highlight the roles and mechanisms of CAFs in promoting carcinogenesis. Ultimately, our aim is to contribute to the development of novel therapeutic strategies for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Observational studies found associations between ankylosing spondylitis (AS) and iridocyclitis (IC), but the causality remained unconfirmed., Methods: We employed two-sample Mendelian randomization (MR) to investigate the bidirectional causal relationships between AS and IC. Single-nucleotide polymorphisms (SNPs) were chosen from the FinnGen database's genome-wide association studies (GWAS) following a rigorous evaluation of the studies' quality. Sensitivity analysis was performed to assess the potential influence of pleiotropy and heterogeneity on the MR findings., Results: Elevated genetic risk for AS showed positive causal effects on IC and its subtypes (IC, OR = 1.094, 95% CI = 1.035-1.157, P = 0.00156; Acute/Subacute IC, OR = 1.327, 95% CI = 1.266-1.392, P = 8.73×10 -32 ; Chronic IC, OR = 1.454, 95% CI = 1.308-1.618, P = 5.19×10 -12 ). Significant causal association was specifically observed between Acute/Subacute IC and AS (OR = 1.944, 95% CI = 1.316-2.873, P = 8.38×10 -4 ). Sensitivity analysis suggested that horizontal pleiotropy was unlikely to influence the causality, and the leave-one-out analysis confirmed that a single SNP did not drive the observed associations., Conclusion: Our findings provide new proof of a positive causal relationship between AS and IC in the European population. Notably, it is Acute/Subacute IC, rather than IC as a whole or Chronic IC, that is associated with an elevated risk of AS. These results emphasize the significance of considering AS characteristics in the diagnosis of Acute/Subacute IC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Xu, Guo, Zhang, Zhou, Wu, Cheng and Guo.)

Competing Interests: Conflicts of interest: We declare no competing interests.