Deciphering RNA m6A regulation in aging: Perspectives on current advances and future directions

N⁶-methyladenosine (m⁶A) is a dynamic and reversible RNA modification that has emerged as a crucial player in the life cycle of RNA, thus playing a pivotal role in various biological processes. In recent years, the potential involvement of RNA m⁶A modification in aging and age-related diseases has gained increasing attention, making it a promising target for understanding the molecular mechanisms underlying aging and developing new therapeutic strategies. This Perspective article will summarize the current advances in aging-related m⁶A regulation, highlighting the most significant findings and their implications for our understanding of cellular senescence and aging, and the potential for targeting RNA m⁶A regulation as a therapeutic strategy. We will also discuss the limitations and challenges in this field and provide insights into future research directions. By providing a comprehensive overview of the current state of the field, this Perspective article aims to facilitate further advances in our understanding of the molecular mechanisms underlying aging and to identify new therapeutic targets for aging-related diseases.     

β‐catenin regulates IRF3‐mediated innate immune signalling in colorectal cancer

Objective

β‐catenin is one of the most critical oncogenes associated with many kinds of human cancers, especially in the human CRC. Innate immunity recognizes tumour derived damage‐associated molecular patterns (DAMPs) and primes the anti‐tumour adaptive responses. While the function of β‐catenin in CRC tumourigenesis is well established, its impact on innate immune evasion is largely unknown. The aim of this study is to characterize the role of β‐catenin in inhibiting RIG‐I‐like receptor (RLR)‐mediated IFN‐β signalling in colorectal cancer.

Materials and Methods

Immunohistochemical staining and western blotting were conducted to study the expression of β‐catenin, IRF3 and phospho‐IRF3 (p‐IRF3) in CRC samples and cell lines. Plaque assay determining virus replication was performed to assess the regulation of β‐catenin on IFN‐β signalling. The inhibition of β‐catenin on RLR‐mediated IFN‐β signalling was further studied by real‐time analyses and reporter assays in the context of lentiviral‐mediated β‐catenin stably knocking down. Lastly, co‐immunoprecipitation and nuclear fractionation assay were conducted to monitor the interaction between β‐catenin and IRF3.

Results

We found that high expression of β‐catenin positively correlated with the expression of IRF3 in CRC cells. Overexpression of β‐catenin increased the viral replication. Conversely knocking down of β‐catenin inhibited viral replication. Furthermore, our data demonstrated that β‐catenin could inhibit the expression of IFN‐β and interferon‐stimulated gene 56 (ISG56). Mechanistically, we found that β‐catenin interacted with IRF3 and blocked its nuclear translocation.

Conclusion

Our study reveals an unprecedented role of β‐catenin in enabling innate immune evasion in CRC.

     

Single-cell transcriptomic atlas of primate cardiopulmonary aging

Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Diseas...     

土壤稳定性有机碳组分与优势细菌门类陆向分布及相关性

【目的】为了探究土壤稳定性有机碳组分和优势细菌门类的陆向分布特征及相关性。【方法】本文选择锡林河流域沿着由水及陆的方向依次采集长期性水流、季节性水流、长期性无水流的湿地及旱地土壤,基于国际腐殖物质协会推荐的方法和16SrRNA基因高通量测序技术分别检测土壤稳定性有机碳组分(富里酸、胡敏酸、胡敏素)含量和优势细菌门类的相对丰度,结合Pearson相关性及冗余分析和结构方程模型研究两者的相关性。【结果】三类稳定性有机碳及酸杆菌门、放线菌门、芽单胞菌门呈大致升高的陆向分布趋势,在长期性无水流的旱地土壤中达到峰值;拟杆菌门则呈现降低的陆向分布趋势。结果显示,芽单胞菌门、酸杆菌门和放线菌门作为长期性无水流旱地土壤的优势细菌门类与胡敏酸、胡敏素含量存在显著(P<0.05)或极显著(P<0.01)正相关关系;拟杆菌门作为长期和季节性水流湿地土壤的优势菌门与富里酸、胡敏酸、胡敏素的含量均呈极显著(P<0.01)负相关关系。结构方程模型结果显示,稳定性有机碳组分与优势细菌门类间存在直接和间接作用。【结论】锡林河流域土壤稳定性有机碳组分及优势细菌门类存在陆向分布特征,稳定性有机碳的升高与...     

Is it necessary for screening irregular antibodies of blood donors?

To explore the necessity of electronic crossmatching applied to irregular antibodies from blood donors, to ensure blood transfusion safety. Irregular antibody screening was performed on blood samples collected in the Dongguan Blood Center from Apr 17, 2014 to Dec 31, 2017. Primary screening was performed on the Sanquin automatic blood group analyzer by the microcolumn gel method (Sanquin). The positive samples were analyzed again using the salt medium method, polybrene method and micro-column gel method (Diana) for the second screening. If the second screening was positive, it was used to determine irregular antibody specificity (using panel cells) and any irregular antibody titer was detected. A total of 208,004 samples were detected, of which 316 were positive (316/208,004; 0.152%). Among them, 120 alloantibodies (120/135,139; 0.088%) were detected in male donors, which was much lower than in female donors (173/72,865; 0.237%) (P<0.01). A total of 16 kinds of known irregular antibodies and 40 cases of unknown antibody specificity were detected, with 119 cases of IgG type and 197 cases of IgM type, at the ratio of 1.65:1. In female donors, the frequencies of anti-D, anti-E, anti-M and anti-Le^a were significantly higher than in male donors (P<0.01). In married couples, the frequencies of anti-D and anti-E were significantly higher than those unmarried (P<0.05). In minority nationalities, the frequency of anti-M was significantly higher than in the Han nationality (P<0.05). In non-Guangdong donors, the frequencies of anti-D and anti-Le^a were significantly higher than in Guangdong donors. 87.02% of irregular antibody positive donors’ antibody titers were lower than “++”, which was deemed as no serious hazard for clinical transfusion. The study suggests that it is unnecessary to screen for irregular antibodies in blood donors. Male donors from Guangdong may not be required to undergo screening for irregular antibodies, and anti-D and anti-E only identification is also not required to be detected in female donors.