The gut microbiota is regarded as the "eighth organ" of the human body and plays a critical regulatory role in the occurrence and progression of various diseases. Ulcerative colitis （UC） is a chronic inflammatory bowel disease with a complex etiology and a tendency toward recurrent episodes. In recent years， studies have shown that gut microbiota dysbiosis plays a key role in its pathological processes. Meanwhile， an increasing number of studies have demonstrated that imbalances in the gut microbiota and abnormalities in its metabolites are closely associated with the development of atrial fibrillation （AF）. Although UC and AF belong to diseases of the digestive system and cardiovascular system， respectively， both exhibit systemic inflammatory characteristics and are often accompanied by gut microbiota dysregulation and abnormal metabolic products. However， systematic investigations into the mechanisms by which gut microbiota-derived metabolites act in these two diseases remain limited. Based on this， the present study adopts literature review and theoretical analysis methods， taking the "gut microbiota-gut-heart" axis as the entry point， to systematically summarize the signaling networks of three key classes of metabolites， i.e.， short-chain fatty acids （SCFAs）， bile acids （BAs）， and trimethylamine N-oxide （TMAO）， in the comorbidity mechanism of UC and AF. The findings indicate that these metabolites may activate key inflammatory pathways， such as NF-κB and NLRP3， thereby synergistically mediating intestinal barrier dysfunction and systemic inflammation and constructing a potential comorbidity network. On this basis， potential intervention strategies for the treatment of UC-AF comorbidity， including probiotic intervention and fecal microbiota transplantation， are further discussed. This study aims to provide new theoretical evidence and research perspectives for prevention and treatment strategies of cross-system diseases.

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.