Ischemic stroke has been reported to cause significant changes to memory, thinking, and behavior. Intriguingly, recently reported studies have indicated the association of Trimethylamine N-oxide (TMAO) with the acute phase of ischemic stroke. However, the comprehensive underlying mechanism remained unknown. The objective of the present study was to investigate the association between TMAO and recovery of neurological function after ischemic stroke. For this purpose, a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established and treated with TMAO or/and sh-ALK5, followed by the neurological function evaluation. Behaviors of rats were observed through staircase and cylinder tests. Moreover, the expression of Smurf2 and ALK5 was detected by immunohistochemistry while expression of GFAP, Neurocan, and Phosphacan in brain tissues was determined by immunofluorescence. Thereafter, gain- and loss-of-function assays in astrocytes, the proliferation, viability, and migration were evaluated by the EdU, CCK-8, and Transwell assays. Besides, Smurf2 mRNA expression was determined by the RT-qPCR, whereas, Smurf2, ALK5, GFAP, Neurocan, and Phosphacan expression was evaluated by the Western blotting. Finally, the interaction of Smurf2 with ALK5 and ALK5 ubiquitination was assessed by the co-immunoprecipitation. Notably, our results showed that TMAO promoted the proliferation of reactive astrocyte and formation of glial scar in MCAO/R rats. However, this effect was abolished by the Smurf2 overexpression or ALK5 silencing. We further found that TMAO upregulated the ALK5 expression by inhibiting the ubiquitination role of Smurf2. Overexpression of ALK5 reversed the inhibitory effect of Smurf2 on astrocyte proliferation, migration, and viability. Collectively, our work identifies the evolutionarily TMAO/Smurf2/ALK5 signaling as a major genetic factor in the control of reactive astrocyte proliferation and glial scar formation in ischemic stroke, thus laying a theoretical foundation for the identification of ischemic stroke.

Purpose:The aim of this study is to visualize and analyze the research hot pots in radiation therapy for rectal cancer and provide researchers with a clear and visual reference for subsequent studies. Methods: The literature scientometric analysis about "external beam radiation therapy (EBRT) for rectal cancer" was made through the WoSCC (2010 to 2019). And the data was visualized and analyzed by the Microsoft Office Excel (2019) and CiteSpace (V. 5.7.R1). Results: 4,263 relevant articles were downloaded. The number of published articles per year has been increasing (2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020). The United States published the highest number of articles. The UK has the strongest partnerships with other countries/regions. Leiden University has the highest number of published articles and University Texas MD Anderson Cancer Center has extensive collaborations with other academic institutions. The number of articles published in the Diseases of the Colon Rectum is the most, and the Journal of Clinical Oncology is the most cited. 27 articles became the strongest burst citations lasting until 2020. In recent years, a lot of research has been done on "watch and wait", "short-course radiotherapy", "MRI", "neoadjuvant radiotherapy, "MRI in rectal cancer", "chemotherapy regimen improvement", "adding adjuvant chemotherapy", and so on. Conclusion:The current research hot pots may be the "watch and wait", "short-course radiotherapy", "MRI", "neoadjuvant chemoradiotherapy", "MRI in rectal cancer", "chemotherapy regimen improvement", and "adding adjuvant chemotherapy".

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