Search

Abstract Objective We aimed to construct a nonlinear regression model through Extreme Gradient Boost (XGBoost) to predict functional outcome 1 year after surgical decompression for patients with acute spinal cord injury (SCI) and explored the importance of predictors in predicting the functional outcome. Methods We prospectively enrolled 249 patients with acute SCI from 5 primary orthopedic centers from June 1, 2016, to June 1, 2020. We identified a total of 6 predictors with three aspects: (1) clinical characteristics, including age, American Spinal Injury Association (ASIA) Impairment Scale (AIS) at admission, level of injury and baseline ASIA motor score (AMS); (2) MR imaging, mainly including Brain and Spinal Injury Center (BASIC) score; (3) surgical timing, specifically comparing whether surgical decompression was received within 24 h or not. We assessed the SCIM score at 1 year after the operation as the functional outcome index. XGBoost was used to build a nonlinear regression prediction model through the method of boosting integrated learning. Results We successfully constructed a nonlinear regression prediction model through XGBoost and verified the credibility. There is no significant difference between actual SCIM and nonlinear prediction model (t = 0.86, P = 0.394; Mean ± SD: 3.31 ± 2.8). The nonlinear model is superior to the traditional linear model (t = 6.57, P

Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m7G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. In addition, METTL1 and WDR4 promote ESCC progression via the tRNA m7G methyltransferase activity in vitro and in vivo. Mechanistically, METTL1 or WDR4 knockdown leads to decreased expression of m7G-modified tRNAs and reduces the translation of a subset of oncogenic transcripts enriched in RPTOR/ULK1/autophagy pathway. Furthermore, ESCC models using Mettl1 conditional knockout and knockin mice uncover the essential function of METTL1 in promoting ESCC tumorigenesis in vivo. Our study demonstrates the important oncogenic function of mis-regulated tRNA m7G modification in ESCC, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for ESCC treatment. Deregulation of METTL1-mediated N7- methylguanosine tRNA modification can promote oncogenesis. Here, the authors report that this modification regulates the translation of proteins in both the mTOR and negative regulators of autophagy pathways, resulting in the progression of esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Limbal stem cells are essential for continuous corneal regeneration and injury repair. METTL3-catalyzed N6-methyladenosine (m6A) mRNA modifications are involved in many biological processes and play a specific role in stem cell regeneration, while the role of m6A modifications in corneal injury repair remains unknown. In this study, we generated a limbal stem cell-specific METTL3 knockout mouse model and studied the role of m6A in repairing corneal injury caused by alkali burn. The results showed that METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DDIT4 as m6A targets. Our study reveals the essential functions of m6A RNA modification in regulating injury repair and provides novel insights for clinical therapy of corneal diseases. [ABSTRACT FROM AUTHOR]

Background : The coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 210 million individuals globally and resulted in over 4 million deaths since the first report in December 2019. The early use of traditional Chinese medicine (TCM) for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have a wide application in treating infectious and non-infectious diseases. Polygonum cuspidatum Sieb. et Zucc. ( P. cuspidatum ), is an important Traditional Chinese Medicine with actions of clearing away heat and eliminating dampness, draining the gallbladder to relieve jaundice, removing blood stasis to alleviate pain, resolving phlegm and arrest cough. In the search for anti-SARS-CoV-2, P. cuspidatum was recommended as as a therapeutic drug of COVID-19 pneumonia.In this study, we aimed to identifies P. cuspidatum is the potential broad-spectrum inhibitor for the treatment of coronaviruses infections. Methods : In the present study , we infected human malignant embryonal rhabdomyoma (RD) cells with the OC43 strain of the coronavirus, which represent an alternative model for SARS-CoV-2 and then employed the cell viability assay kit for the antiviral activity. We combined computer aided virtual screening to predicte the binding site and employed Surface plasmon resonance analysis (SPR) to comfirm the interaction between drugs and coronavirus. We employed fluorescence resonance energy transfer technology to identify drug's inhibition in the proteolytic activity of 3CLpro and Plpro. Results : Based on our results, polydatin and resveratrol derived from P. cuspidatum significantly suppressed HCoV-OC43 replication. 50% inhibitory concentration (IC 50 ) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 μm, respectively. IC 50 values of resveratrol inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 29.81 ,60.86, 16.35 and19.04 μM, respectively. Finally, SPR assay confirmed that polydatin and resveratrol had high affinity to SARS-CoV-2, SARS-CoV 3Clpro, MERS-CoV 3Clpro and PLpro protein. Conclusions : we identified the antiviral activity of flavonoids polydatin and resveratrol on RD cells. Polydatin and resveratrol were found to be specific and selective inhibitors for SARS-CoV-2, 3CLpro and PLpro, viral cysteine proteases. In summary, this study identifies P. cuspidatum as the potential broad-spectrum inhibitor for the treatment of coronaviruses infections., (© 2021 The Author(s). Published by BRI.)

Limbal stem cells are essential for continuous corneal regeneration and injury repair. METTL3-catalyzed N6-methyladenosine (m 6 A) mRNA modifications are involved in many biological processes and play a specific role in stem cell regeneration, while the role of m 6 A modifications in corneal injury repair remains unknown. In this study, we generated a limbal stem cell-specific METTL3 knockout mouse model and studied the role of m 6 A in repairing corneal injury caused by alkali burn. The results showed that METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m 6 A modification profiling identified stem cell regulatory factors AHNAK and DDIT4 as m 6 A targets. Our study reveals the essential functions of m 6 A RNA modification in regulating injury repair and provides novel insights for clinical therapy of corneal diseases., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Yarong Dai et al.)

The coronavirus disease 2019 (COVID-19) is a new type of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. COVID-19 is affecting millions of patients, and the infected number keeps increasing. SARS-CoV-2 is highly infectious, has a long incubation period, and causes a relatively high death rate, resulting in severe health problems all over the world. Currently there is no effective proven drug for the treatment of COVID-19; therefore, development of effective therapeutic drugs to suppress SARS-CoV-2 infection is urgently needed. In this review, we first summarize the structure and genome features of SARS-CoV-2 and introduce its infection and replication process. Then, we review the clinical symptoms, diagnosis, and treatment options of COVID-19 patients. We further discuss the potential molecular targets and drug development strategies for treatment of the emerging COVID-19. Finally, we summarize clinical trials of some potential therapeutic drugs and the results of vaccine development. This review provides some insights for the treatment of COVID-19., (© 2020 The Author(s).)