The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

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Cytokinins (CKs), a class of phytohormone, regulate root growth in a dose-dependent manner. A certain threshold content of CK is required for rapid root growth, but supraoptimal CK content inhibits root growth, and the mechanism of this inhibition remains unclear in rice. In this study, treatments of lovastatin (an inhibitor of CK biosynthesis) and kinetin (KT; a synthetic CK) were found to inhibit rice seminal root growth in a dose-dependent manner, suggesting that endogenous CK content is optimal for rapid growth of the seminal root in rice. KT treatment strongly increased ethylene level by upregulating the transcription of ethylene biosynthesis genes. Ethylene produced in response to exogenous KT inhibited rice seminal root growth by reducing meristem size via upregulation of OsIAA3 transcription and reduced cell length by downregulating transcription of cell elongation-related genes. Moreover, the effects of KT treatment on rice seminal root growth, root meristem size and cell length were rescued by treatment with aminoethoxyvinylglycine (an inhibitor of ethylene biosynthesis), which restored ethylene level and transcription levels of OsIAA3 and cell elongation-related genes. Supraoptimal CK content increases ethylene level by promoting ethylene biosynthesis, which in turn inhibits rice seminal root growth by reducing root meristem size and cell length.

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HighlightsOverexpression of miR-519a is observed in HCC tissues.High expression of miR-519a is associated with adverse clinicopathologic features and reduced survival of HCC patients.MiR-519a promotes proliferation and inhibits apoptosis in HCC cells.FOXF2 is a direct downstream target of miR-519a in HCC.FOXF2 functions in elevated miR-519a-induced HCC cell growth.

Background Elderly patients with COVID-19 were shown to have a high case-fatality rate. We aimed to explore the risk factors associated with death in patients over 70 years old (yr). Methods In this retrospective study, we enrolled consecutively hospitalized patients over 70 yr with COVID-19 between January 20 and February 15, 2020 in Renmin Hospital of Wuhan University. Epidemiological, demographic, and clinical data were collected. Clinical subtypes, including mild, moderate, severe, and critical types, were used to evaluate the severity of disease. Patients were classified into two groups: survivor and non-survivor groups. Clinical data were compared between the two groups. Univariable and multivariable Cox regression methods were used to explore the risk factors. Results A total of 147 patients were enrolled. The case-fatality rate was 28.6%. Multivariable Cox proportional hazard regression showed that clinical subtypes, including the severe type (HR = 2.983, 95% CI: 1.231–7.226, P = 0.016) and the critical type (HR = 3.267, 95%CI: 1.009–10.576, P = 0.048), were associated with increasing risk of death when compared with the general type. Blood urea nitrogen greater than 9.5 mmol/L (HR = 2.805, 95% CI: 1.141–6.892, P = 0.025) on admission was an independent risk factor for death among laboratory findings. Conclusion The patients over 70 yr with COVID-19 had a high case-fatality rate. The risk factors, including clinical subtypes and blood urea nitrogen greater than 9.5 mmol/L, could help physicians to identify elderly patients with poor clinical outcomes at an early stage.

Interferon-alpha (IFN-α) and nucleot(s)ide analogs (NAs) are first-line drugs for the treatment of chronic hepatitis B virus (HBV) infections. Generally, NAs target the reverse transcription of HBV pregenomic RNA, but they cannot eliminate covalently-closed-circular DNA (cccDNA). Although effective treatment with NAs can dramatically decrease HBV proteins and DNA loads, and even promote serological conversion, cccDNA persists in the nucleus of hepatocytes due to the lack of effective anti-cccDNA drugs. Of the medications currently available, only IFN-α can potentially target cccDNA. However, the clinical effects of eradicating cccDNA using IFN-α in the hepatocytes of patients with HBV are not proficient as well as expected and are not well understood. Herein, we review the anti-HBV mechanisms of IFN-α involving cccDNA modification as the most promising approaches to cure HBV infection. We expect to find indications of promising areas of research that require further study to eliminate cccDNA of HBV in patients.