Yong Yuan

Abstract Animal studies have indicated that SOX10 is one of the key transcription factors regulating the proliferation, migration and differentiation of multipotent neural crest (NC), and mutation of SOX10 in humans may lead to type 4 Waardenburg syndrome (WS). However, the exact role of SOX10 in human NC development and the underlying molecular mechanisms of SOX10-related human diseases remain poorly understood due to the lack of appropriate human model systems. In this study, we successfully generated SOX10-knockout human induced pluripotent stem cells (SOX10 −/− hiPSCs) by the CRISPR-Cas9 gene editing tool. We found that loss of SOX10 significantly inhibited the generation of p75 high HNK1 + /CD49D + postmigratory neural crest stem cells (NCSCs) and upregulated the cell apoptosis rate during NC commitment from hiPSCs. Moreover, we discovered that both the neuronal and glial differentiation capacities of SOX10 −/− NCSCs were severely compromised. Intriguingly, we showed that SOX10 −/− hiPSCs generated markedly more TFAP2C + nonneural ectoderm cells (NNE) than control hiPSCs during neural crest differentiation. Our results indicate that SOX10 is crucial for the transition of premigratory cells to migrating NC and is vital for NC survival. Taken together, these results provide new insights into the function of SOX10 in human NC development, and the SOX10-knockout hiPSC lines may serve as a valuable cell model to study the pathogenesis of SOX10-related human neurocristopathies.

The efficacy of COVID-19 vaccines varies between individuals and populations, and the reasons for this are still not fully understood. Recent clinical studies and animal models have indicated that the gut microbiota may influence the immunogenicity of the vaccine and, thus, its effectiveness. This suggests that there is a bidirectional relationship between the gut microbiota and the COVID-19 vaccine, with the varying components of the microbiota either enhancing or reducing the vaccine's efficacy. To put an end to the spread of the COVID-19 pandemic, the necessity of vaccines that create powerful and long-term immunity is now more important than ever, and understanding the role of the gut microbiota in this process is essential. Conversely, COVID-19 vaccines also have a significant effect on the gut microbiota, decreasing its total number of organisms and the variety of species present. In this Review, we analyze the evidence that suggesting an interaction between the gut microbiota and COVID-19 vaccine effectiveness, consider the immunological mechanisms that may be responsible for this connection, and explore the possibility of using gut microbiota-focused interventions to improve the efficacy of COVID-19 vaccines.

All-trans retinoic acid (ATRA) is a potent chemopreventive and therapeutic agent and exerts its effects by inducing growth arrest. In the present study, we demonstrated that ATRA activated the expression of p53 via Axin and induced cell cycle arrest at the G1/S phase and apoptosis of glioma cells. Briefly, C6 cells were treated with ATRA, and the levels of p53 mRNA and protein were determined by RT-PCR, western blotting and immunohistochemistry. The results showed that ATRA activated the expression of p53. In addition, ectopic expression of Axin by transient transfection of C6 cells with rAxin revealed that overexpression of Axin induced cell cycle arrest and apoptosis with an upregulation of p53. Furthermore, loss-of-function of Axin in glioma cells by RNAi blocked ATRA-induced cell cycle phase arrest and apoptosis via downregulation of p53. The present study revealed a novel function of Axin and identified it as an important regulator of ATRA-activated p53 expression.

BACKGROUND: Lower limb ischemia in patients with extracorporeal membrane oxygenation (ECMO) via femoral artery catheterization negatively affects patient mortality and survivors' quality of life [Gulkarov 2020]. In this study, ECMO was established via femoral artery catheterization. This study aimed to identify the risk factors of lower limb ischemia to provide sufficient evidence for its prevention. METHODS: All patients with venoarterial (VA) ECMO via femoral artery catheterization in Zhongshan People's Hospital from January 2008 to November 2019 retrospectively were analyzed. Patients' general information and ECMO-related information were obtained, and the main outcome variables were survival and discharge and intubation-related adverse events (limb ischemia and incision bleeding). Logistic regression analysis was used to determine the independent risk factors of limb ischemia in patients with VA ECMO. RESULTS: A total of 179 (98 [54.7%] men and 81 [45.3%] women) eligible patients were included in this study. Moreover, a total of 90 patients (48.9%) had low cardiac output, 41 (22.3%) had acute myocardial infarction, and 33 (17.9%) had fulminant myocarditis. Eighty-six (48.04%) patients survived to hospital discharge, 36 (20.11%) had limb ischemia, and 42 (23.46%) had incision bleeding. Furthermore, the ECMO-assisted time was 114.23 ± 67.88 hours. There was no significant difference in age, sex, and Sequential Organ Failure Assessment score between the limb ischemia group and the non-limb ischemia group. Multivariate logistic regression analysis showed that peripheral artery disease (odds ratio, 27.12; 95% confidence interval, 5.614-130.96) was an independent risk factor of limb ischemia in patients with ECMO. CONCLUSION: Limb ischemia is a common complication in patients with VA ECMO, and peripheral artery disease is an independent risk factor of limb ischemia in patients with VA ECMO via femoral artery catheterization.