BACKGROUND Targeting DNA damage response(DDR)pathway is a cutting-edge strategy.It has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in DDR.However,the detailed mechan...BACKGROUND Targeting DNA damage response(DDR)pathway is a cutting-edge strategy.It has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in DDR.However,the detailed mechanism is unclear.AIM To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects.METHODS To reach the purpose,eight esophageal squamous carcinoma cell lines,142 esophageal dysplasia(ED)and 1007 primary esophageal squamous cell carcinoma(ESCC)samples and various techniques were utilized,including methylationspecific polymerase chain reaction,CRISPR/Cas9 technique,Western blot,colony formation assay,and xenograft mouse model.RESULTS Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of primary(258/1007)ESCC cases,and its expression was regulated by promoter region methylation.SLFN11 methylation was significantly associated with tumor differentiation and tumor size(both P<0.05).However,no significant associations were observed between promoter region methylation and age,gender,smoking,alcohol consumption,TNM stage,or lymph node metastasis.Utilizing DNA damaged model induced by low dose cisplatin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways,while inhibiting the ATM/CHK2 signaling pathway.Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in vivo.CONCLUSION SLFN11 is frequently methylated in human ESCC.Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.展开更多
AIM: To investigate the effects of baffle and intraocular pressure(IOP) on the aerosols generated in the noncontact tonometer(NCT) measurement and provide recommendations for the standardized use of the NCT during cor...AIM: To investigate the effects of baffle and intraocular pressure(IOP) on the aerosols generated in the noncontact tonometer(NCT) measurement and provide recommendations for the standardized use of the NCT during coronavirus disease 2019(COVID-19). METHODS: This clinical trial included 252 subjects(312 eyes) in The Eye Hospital, Wenzhou Medical University from March 7, 2020, to March 28, 2020. Sixty subjects(120 eyes) with normal IOP were divided into two groups. One group used an NCT without a baffle, another group used an NCT with a baffle. Another 192 subjects(192 eyes) were divided into four groups: Group A;(without a baffle+normal IOP), Group A;(without a baffle+high IOP), Group B;(with a baffle+normal IOP) and Group B;(with a baffle+high IOP). Particulate matter(PM) 2.5 and PM10 generated by all subjects were quantified during the NCT measurement. The IOP values were recorded simultaneously. Effects of baffle and IOP on aerosols generated during the NCT measurement were analyzed.RESULTS: In the normal eye group with a baffle, the aerosol density decreased in a wave-like shape near the NCT with the increase in the number of people measured for IOP, demonstrating no cumulative effect. However, in the normal eye group without a baffle, there was a cumulative effect. PM2.5 and PM10 in Group A;were higher than Group A;(both P<0.001). The PM2.5 and PM10 in Group B;were higher than Group B;(P<0.01, P<0.001 respectively). The PM10 of Group B;was lower than Group A;(P<0.01). PM2.5 in Group B;were lower than Group A;(P<0.01). The median of per capita PM2.5 and PM10 in the combined Group A;+A;were 0.80 and 1.10 μg/m;respectively, which were higher than 0.20 and 0.60 μg/m;in the combined Group B;+B;(both P<0.01). The median of per capita PM2.5 and PM10 in the combined Group A;+B;were 0.10 and 0.20 μg/m;respectively, which were lower than 1.30 and 1.70 μg/m;in the combined Group A;+B;(both P<0.001).CONCLUSION: More aerosols could be generated in patients with high IOP. After the NCT is equipped with a baffle, per c展开更多
Density functional theory was used to study the NH3 behavior on Ni monolayer covered Pt（111） and WC（001）. The electronic structure of the surfaces, and the adsorption and decomposition of NH3 were calculated and c...Density functional theory was used to study the NH3 behavior on Ni monolayer covered Pt（111） and WC（001）. The electronic structure of the surfaces, and the adsorption and decomposition of NH3 were calculated and compared. Ni atoms in the monolayer behave different from that in Ni（111）. More dz2 electrons of Ni in monolayer covered systems were shifted to other regions compared to Ni（111）, charge density depletion on this orbital is crucial to NH3 adsorption. NH3 binds more stable on Ni/Pt（lll） and Ni/WC（001） than on Ni（111）, the energy barriers of the first N-H bond scission were evidently lower on Ni/Pt（111） and Ni/WC（001） than on Ni（111）, these are significant to NH3 decomposition. N recombination is the rate-limiting step, high reaction barrier implies that N2 is produced only at high temperatures. Although WC has similar properties to Pt, differences of the electronic structure and catalytic activities are observed for Ni/Pt（111） and Ni/WC （001）, the energy barrier for the rate-determined step increases on Ni/WC（001） instead of decreasing on Ni/Pt（lll） when compared to Ni（111）. the N recombination barrier by modifying To design cheaper and better catalysts, reducing Ni/WC（001） is a critical question to be solved.展开更多
基金Supported by the National Key Research and Development Program of China,No.2018YFA0208902National Science Foundation of China,No.82272632,No.81672318,and No.U1604281+1 种基金Beijing Science Foundation of China,No.7171008Youth Innovation Science Foundation of Chinese PLA General Hospital,No.22QNCZ027.
文摘BACKGROUND Targeting DNA damage response(DDR)pathway is a cutting-edge strategy.It has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in DDR.However,the detailed mechanism is unclear.AIM To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects.METHODS To reach the purpose,eight esophageal squamous carcinoma cell lines,142 esophageal dysplasia(ED)and 1007 primary esophageal squamous cell carcinoma(ESCC)samples and various techniques were utilized,including methylationspecific polymerase chain reaction,CRISPR/Cas9 technique,Western blot,colony formation assay,and xenograft mouse model.RESULTS Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of primary(258/1007)ESCC cases,and its expression was regulated by promoter region methylation.SLFN11 methylation was significantly associated with tumor differentiation and tumor size(both P<0.05).However,no significant associations were observed between promoter region methylation and age,gender,smoking,alcohol consumption,TNM stage,or lymph node metastasis.Utilizing DNA damaged model induced by low dose cisplatin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways,while inhibiting the ATM/CHK2 signaling pathway.Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in vivo.CONCLUSION SLFN11 is frequently methylated in human ESCC.Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.
文摘AIM: To investigate the effects of baffle and intraocular pressure(IOP) on the aerosols generated in the noncontact tonometer(NCT) measurement and provide recommendations for the standardized use of the NCT during coronavirus disease 2019(COVID-19). METHODS: This clinical trial included 252 subjects(312 eyes) in The Eye Hospital, Wenzhou Medical University from March 7, 2020, to March 28, 2020. Sixty subjects(120 eyes) with normal IOP were divided into two groups. One group used an NCT without a baffle, another group used an NCT with a baffle. Another 192 subjects(192 eyes) were divided into four groups: Group A;(without a baffle+normal IOP), Group A;(without a baffle+high IOP), Group B;(with a baffle+normal IOP) and Group B;(with a baffle+high IOP). Particulate matter(PM) 2.5 and PM10 generated by all subjects were quantified during the NCT measurement. The IOP values were recorded simultaneously. Effects of baffle and IOP on aerosols generated during the NCT measurement were analyzed.RESULTS: In the normal eye group with a baffle, the aerosol density decreased in a wave-like shape near the NCT with the increase in the number of people measured for IOP, demonstrating no cumulative effect. However, in the normal eye group without a baffle, there was a cumulative effect. PM2.5 and PM10 in Group A;were higher than Group A;(both P<0.001). The PM2.5 and PM10 in Group B;were higher than Group B;(P<0.01, P<0.001 respectively). The PM10 of Group B;was lower than Group A;(P<0.01). PM2.5 in Group B;were lower than Group A;(P<0.01). The median of per capita PM2.5 and PM10 in the combined Group A;+A;were 0.80 and 1.10 μg/m;respectively, which were higher than 0.20 and 0.60 μg/m;in the combined Group B;+B;(both P<0.01). The median of per capita PM2.5 and PM10 in the combined Group A;+B;were 0.10 and 0.20 μg/m;respectively, which were lower than 1.30 and 1.70 μg/m;in the combined Group A;+B;(both P<0.001).CONCLUSION: More aerosols could be generated in patients with high IOP. After the NCT is equipped with a baffle, per c
文摘Density functional theory was used to study the NH3 behavior on Ni monolayer covered Pt（111） and WC（001）. The electronic structure of the surfaces, and the adsorption and decomposition of NH3 were calculated and compared. Ni atoms in the monolayer behave different from that in Ni（111）. More dz2 electrons of Ni in monolayer covered systems were shifted to other regions compared to Ni（111）, charge density depletion on this orbital is crucial to NH3 adsorption. NH3 binds more stable on Ni/Pt（lll） and Ni/WC（001） than on Ni（111）, the energy barriers of the first N-H bond scission were evidently lower on Ni/Pt（111） and Ni/WC（001） than on Ni（111）, these are significant to NH3 decomposition. N recombination is the rate-limiting step, high reaction barrier implies that N2 is produced only at high temperatures. Although WC has similar properties to Pt, differences of the electronic structure and catalytic activities are observed for Ni/Pt（111） and Ni/WC （001）, the energy barrier for the rate-determined step increases on Ni/WC（001） instead of decreasing on Ni/Pt（lll） when compared to Ni（111）. the N recombination barrier by modifying To design cheaper and better catalysts, reducing Ni/WC（001） is a critical question to be solved.
