Hui and Fu contributed equally to the work.Ye and Cai contributed equally to the work.

No abstract

Molecular characterizations, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) showed strong associations in colorectal carcinoma (CRC) and provided a deeper understanding of the etiology of disease. However, the global relationship between epigenetic alternations and changes in mRNA expression in CRC remains largely undefined, especially regarding the roles of DNA methyltransferases (DNMTs). Here, we conducted a systematic network comparison to explore the global conservation between co-expressed and co-methylated modules. We successfully identified immune-related modules that were regulated by DNMTs and had strong associations with immune-infiltrating neutrophils and dendritic cells in CRC. Moreover, we found that genes in those modules were prognostic for CRC, with 97.1% (168/ 173) being significantly influenced by DNMTs. Thus, this study resolved an interaction between DNA methylation and mRNA expression through DNMTs. Additionally, we provided evidence that DNMTs control the global hypomethylation of oncogenes, including ALOX5AP and CSF3R that otherwise have high methylation in normal colons. Such genes were also more sensitive to DNMT changes, such as in CRC. Collectively, our analyzes provided a systems biology approach to investigate the association among different molecular phenotypes in diseases.

Background The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID‐19. Methods A total of 126 COVID‐19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. Results 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08–10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53–7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04–6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04–4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86–0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02–1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3−CD56+ NK cells (OR, 0.87; 95% CI, 0.76–0.99) were related with prolonged fecal shedding. Conclusions Obesity, delayed antiviral treatment, and positive SARS‐CoV‐2 for stool were independent risk factors for prolonged SARS‐CoV‐2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.