AIM： To compare the volumetric-modulated arc ther- apy （VMAT） plans with conventional sliding window intensity-modulated radiotherapy （c-IMRT） plans in esophageal cancer （EC）. METHODS： Twenty patients with EC ...AIM： To compare the volumetric-modulated arc ther- apy （VMAT） plans with conventional sliding window intensity-modulated radiotherapy （c-IMRT） plans in esophageal cancer （EC）. METHODS： Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning sys- tem： three using c-IMRT with 5 fields （5F）, 7 fields （7F） and 9 fields （gF）, and two using VMAT with a single arc （1A） and double arcs （2A）. The treatment plans were designed to deliver a dose of 60 Gy to the plan-ning target volume （PTV） with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normal- ized to 95% of the PTV that received 100% of the pre- scribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk （OAR） such as lungs, spinal cord and heart. Monitor units （MU） and normal tissue complication probability （NTCP） of OAR were also reported. RESULTS： Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different Io- cations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions： in cervical and upper thoracic EC, the conformity index （CI） was higher in VMAT （1A 0.78 and 2A 0.8） than in c-IMRT （5F 0.62, 7F 0.66 and 9F 0.73） and homogeneity was slightly better in c-IMRT （7F 1.09 and 9F 1.07） than in VMAT （1A 1,1 and 2A 1.09）, Lung V30 was lower in VMAT （1A 12.52 and 2A 12.29） than in c-IMRT （7F 14.35 and 9F 14.81）. The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT （1A 0.76 and 2A 0.74） was higher than in c-IMRT （5F 0.63 Gy and 7F 0.67 Gy）, and homogeneity was almost similar between VMAT and c-IMRT展开更多
A research with Bacillus mucilaginosus cultured in nitrogen-free medium for forming a flocculant material to adsorb Cr+6 was conducted to determine the effects of different pH, volume, treatment time, and chromium (VI...A research with Bacillus mucilaginosus cultured in nitrogen-free medium for forming a flocculant material to adsorb Cr+6 was conducted to determine the effects of different pH, volume, treatment time, and chromium (VI) concentrations on chromium (VI) adsorption by microbial flocculant (MBF), which was produced from the B. mucilaginosus GY03 strain. The results showed that MBF had outstanding flocculation on chromium (VI). Based on the results of a oneway experiment and actual wastewater treatment conditions, the optimum conditions, obtained by using orthogonal experiments, for chromium (VI) adsorption by MBF were: Cr6+ solution pH of 9, flocculant material volume of 15 mL, treatment time of 12 h and chromium ion concentration of 30 mg L-1. The results demonstrated that the MBF produced from GY03 could be used in the chromium-containing wastewater treatment. Meanwhile, after extraction and analysis of the MBF polysaccharides, it was found that MBF was mainly composed of glycoprotein. Analysis on constituents of monosaccharide showed that polysaccharides of B. mucilaginosus were composed of rhamnose, glucose etc. Thus, because it was applied over a wide range of pH, in small amounts and had a rapid flocculation speed the flocculant used in this experiment had a vast field of application potential.展开更多
Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. ...Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8 a(IC50=3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound 15 u(IC50=49 nmol/L, and Ki= 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3 K4 me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency ofcompound 15 u. Compound 15 u also showed strong antiproliferative activity against four leukemia cell lines(OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, 15 u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15 u induced expression of CD86 and CD11 b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation.The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazolefused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1 A inhibitors.展开更多
基金Supported by The National Natural Science Foundation of China, No. 30870738
文摘AIM： To compare the volumetric-modulated arc ther- apy （VMAT） plans with conventional sliding window intensity-modulated radiotherapy （c-IMRT） plans in esophageal cancer （EC）. METHODS： Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning sys- tem： three using c-IMRT with 5 fields （5F）, 7 fields （7F） and 9 fields （gF）, and two using VMAT with a single arc （1A） and double arcs （2A）. The treatment plans were designed to deliver a dose of 60 Gy to the plan-ning target volume （PTV） with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normal- ized to 95% of the PTV that received 100% of the pre- scribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk （OAR） such as lungs, spinal cord and heart. Monitor units （MU） and normal tissue complication probability （NTCP） of OAR were also reported. RESULTS： Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different Io- cations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions： in cervical and upper thoracic EC, the conformity index （CI） was higher in VMAT （1A 0.78 and 2A 0.8） than in c-IMRT （5F 0.62, 7F 0.66 and 9F 0.73） and homogeneity was slightly better in c-IMRT （7F 1.09 and 9F 1.07） than in VMAT （1A 1,1 and 2A 1.09）, Lung V30 was lower in VMAT （1A 12.52 and 2A 12.29） than in c-IMRT （7F 14.35 and 9F 14.81）. The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT （1A 0.76 and 2A 0.74） was higher than in c-IMRT （5F 0.63 Gy and 7F 0.67 Gy）, and homogeneity was almost similar between VMAT and c-IMRT
基金Project supported by the Chinese Academy of Sciences (No. HDH010901) the China Postdoctoral Science Foundation (No. 2003033496) the Funds for Attracting Talents of Nanjing Normal University (No. 184070H2B39).
文摘A research with Bacillus mucilaginosus cultured in nitrogen-free medium for forming a flocculant material to adsorb Cr+6 was conducted to determine the effects of different pH, volume, treatment time, and chromium (VI) concentrations on chromium (VI) adsorption by microbial flocculant (MBF), which was produced from the B. mucilaginosus GY03 strain. The results showed that MBF had outstanding flocculation on chromium (VI). Based on the results of a oneway experiment and actual wastewater treatment conditions, the optimum conditions, obtained by using orthogonal experiments, for chromium (VI) adsorption by MBF were: Cr6+ solution pH of 9, flocculant material volume of 15 mL, treatment time of 12 h and chromium ion concentration of 30 mg L-1. The results demonstrated that the MBF produced from GY03 could be used in the chromium-containing wastewater treatment. Meanwhile, after extraction and analysis of the MBF polysaccharides, it was found that MBF was mainly composed of glycoprotein. Analysis on constituents of monosaccharide showed that polysaccharides of B. mucilaginosus were composed of rhamnose, glucose etc. Thus, because it was applied over a wide range of pH, in small amounts and had a rapid flocculation speed the flocculant used in this experiment had a vast field of application potential.
基金supported by the National Key Research Program of Proteins(Nos.2016YFA0501800 and 2017YFD0501401,China)the National Natural Science Foundation of China(Nos.81703326,81773562,81430085 and 21403200,China)+5 种基金the Open Fund of State Key Laboratory of Pharmaceutical Biotechnology,Nan-jing University,China(No.KF-GN-201902,China)Outstanding Young Talent Research Fund of Zhengzhou University(No.1521331002,China)Scientific Program of Henan Province(Nos.182102310123 and 161100310100,China)China Postdoctoral Science Foundation(No.2018M630840,China)Key Research Program of Higher Education of Henan Province(Nos.15A350018 and 18B350009,China)the Starting Grant of Zhengzhou University(No.32210533,China)
文摘Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8 a(IC50=3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound 15 u(IC50=49 nmol/L, and Ki= 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3 K4 me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency ofcompound 15 u. Compound 15 u also showed strong antiproliferative activity against four leukemia cell lines(OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, 15 u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15 u induced expression of CD86 and CD11 b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation.The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazolefused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1 A inhibitors.
