In a survey on the Yellow Sea and the East China Sea on August 20-30 of 1999,we found a hypoxic zone(<2 mg/L)of 13700 km2 with an average thickness of 20m at the bottom of the Changjiang(Yangtze River)Estuary,with ...In a survey on the Yellow Sea and the East China Sea on August 20-30 of 1999,we found a hypoxic zone(<2 mg/L)of 13700 km2 with an average thickness of 20m at the bottom of the Changjiang(Yangtze River)Estuary,with an oxygen minimum value of 1 mg/L.The extension of the dissolved oxygen deficiency extended to the 100m isobath in a southeastward direction along the bottom of the continental shelf of the East China Sea.During the last two decades,the minimum dissolved oxygen values in the low oxygen region of the Changjiang Estuary have decreased from 2.85 mg/L to 1 mg/L.In the hypoxic zone,the apparent oxygen utilization(AOU)was 5.8 mg/L and the total oxygen depletion approximately 1.59×10^(6) t.The strong halocline above the hypoxic zone,as a result of affluent water from the Changjiang,Taiwan Warm Current(TWC),and the high concentrations of particle organic carbon(POC)and nitrogen(PON)are the major factors causing the formation of the hypoxic zone.The POC:PON ratios and nutrient concentration distributions in the hypoxic zone suggest that the oxygen deficiency in the bottom water during the summer in the East China Sea off the Changjiang is the result of organic carbon production enhanced by nutrients from the Changjiang and fluvial organic matter input,followed by a shift in regeneration of nutrients in the East China Sea.展开更多
At the present paper,adult populations of the psocid, Liposcelis bostrychophila ,were exposed respectively for 30 generations to two atmospheres containing 0 5% and 1% O 2 (N 2 in mixture as balance),in order to...At the present paper,adult populations of the psocid, Liposcelis bostrychophila ,were exposed respectively for 30 generations to two atmospheres containing 0 5% and 1% O 2 (N 2 in mixture as balance),in order to select strains resistant to low O 2 content (LOC) atmosphere.Selection pressure was maintained at around 70% mortality.At the 30th generation,comparison of sensitivity between the selected strains (LOC1 and LOC2) and the original susceptible strain (CA S) indicated a tolerance factor (TF) at the 50% mortality level (LT 50 ) of 4 7 and 3 9 fold,respectively.Throughout the selection process,log time against probit mortality lines remained roughly parallel and the slopes remained lower than that of CA S strain until the last generation.The implication is that at high level of selection,multiple genetic factors continued act together even at the 30th generation to select for adaptation to survival at depleted O 2 concentration.Up to 30th generation,two selected strains still possessed the genetic potential to develop resistance to LOC.Removal of selection pressure for 5 generations from 2 sub populations of two selected strains from 25th generation caused significant reduction in resistance.In the absence of CA exposure,the two selected strains all possessed the reproductive disadvantages or fitness defect.LOC1 and LOC2 were calculated by R 0 to have a fitness value of 0 56 and 0 75 relative to unselected strain,respectively.展开更多
Our study investigated the role of oxygen in mediating the FLASH efect.This efect,which was frst reported in vitro in the 1950s and in vivo in the 1970s,recently gained prominence with a number of publications showing...Our study investigated the role of oxygen in mediating the FLASH efect.This efect,which was frst reported in vitro in the 1950s and in vivo in the 1970s,recently gained prominence with a number of publications showing diferential sparing between normal tissues and tumors.Oxygen depletion(and subsequent induction of transient hypoxia)is the oldest and most prominent hypothesis to explain this efect.To better understand how the oxygen depletion hypothesis and oxygen enhancement ratio(OER)are relevant for interpreting FLASH benefts,an analytical model was proposed to estimate the sparing factor.The model incorporated factors such as OER,oxygen partial pressure(pO_(2)),loco-regional oxygen difusion/metabolism,total dose and dose rate.The sparing factor,was used to quantify the sparing of normal tissue(initially physoxic).The radiosensitivity parameters of two cell types(V79 Chinese hamster cells and T1 human kidney cells)were selected.Furthermore,the transient behavior of OER during fnite time intervals was modeled,for both without and with the presence of oxygen transport using a difusion model.For tissues with an oxygen consumption rate of 20mmHg/s and a distance of 60μm away from blood vessels,the sparing factor demonstrates an increase from 1.03/1.06(V79/T1)at 2.5Gy/s up to 1.28/1.72(V79/T1)at 100Gy/s(total dose:10Gy).For normal tissues of initial pO_(2) between 1.5 and 8mmHg,the beneft from pushing the dose rate above 100Gy/s is found to be marginal.Preliminary animal experiments have been conducted for validation.Overall,our study predicts that the dose rate associated with maximum normal tissue protection is between 50Gy/s and 100Gy/s.Other than the postulation of the hypoxic stem cell niches in normal tissues,we believe that a framework based upon the oxygen depletion hypothesis and OER is not able to efciently interpret diferential responses between normal and tumor tissue under FLASH irradiation.展开更多
FLASH radiotherapy(FLASH-RT)is a new strategy for tumor treatment with an ultra-high dose rate of more than 40 Gy/s.Compared with conventional radiotherapy(CONV-RT),FLASH-RT has no different inhibitory effects on tumo...FLASH radiotherapy(FLASH-RT)is a new strategy for tumor treatment with an ultra-high dose rate of more than 40 Gy/s.Compared with conventional radiotherapy(CONV-RT),FLASH-RT has no different inhibitory effects on tumors but less damage to normal tissues,which is called the“spare”effect.The“spare”effect triggers our exploration of the great prospect of subverting conventional radiotherapy and its intricate mechanisms.Mitochondrial homeostasis,the immune microenvironment,or DNA integrity may potentially represent the primary breakthrough direction in understanding the mechanisms.Concurrently,it is imperative to advance timely clinical translation efforts.Clinical trials of FLASH-RT have progressed to Phase II in both the United States and Switzerland,with current findings suggesting that FLASH-RT achieves comparable efficacy to CONV-RT while mitigating side effects in select cancer cell types.While summarizing the existing FLASH experiments,this paper emphasizes the significance of clinical transformation and the challenges that will be faced and proposes possible solutions.展开更多
基金This study was made under the auspices of the National Key Basic Research Program of the Ministry of Science and Technology,P.R.China(Grant No.G1999043705)and the Shanghai Priority Academic Discipline.
文摘In a survey on the Yellow Sea and the East China Sea on August 20-30 of 1999,we found a hypoxic zone(<2 mg/L)of 13700 km2 with an average thickness of 20m at the bottom of the Changjiang(Yangtze River)Estuary,with an oxygen minimum value of 1 mg/L.The extension of the dissolved oxygen deficiency extended to the 100m isobath in a southeastward direction along the bottom of the continental shelf of the East China Sea.During the last two decades,the minimum dissolved oxygen values in the low oxygen region of the Changjiang Estuary have decreased from 2.85 mg/L to 1 mg/L.In the hypoxic zone,the apparent oxygen utilization(AOU)was 5.8 mg/L and the total oxygen depletion approximately 1.59×10^(6) t.The strong halocline above the hypoxic zone,as a result of affluent water from the Changjiang,Taiwan Warm Current(TWC),and the high concentrations of particle organic carbon(POC)and nitrogen(PON)are the major factors causing the formation of the hypoxic zone.The POC:PON ratios and nutrient concentration distributions in the hypoxic zone suggest that the oxygen deficiency in the bottom water during the summer in the East China Sea off the Changjiang is the result of organic carbon production enhanced by nutrients from the Changjiang and fluvial organic matter input,followed by a shift in regeneration of nutrients in the East China Sea.
文摘At the present paper,adult populations of the psocid, Liposcelis bostrychophila ,were exposed respectively for 30 generations to two atmospheres containing 0 5% and 1% O 2 (N 2 in mixture as balance),in order to select strains resistant to low O 2 content (LOC) atmosphere.Selection pressure was maintained at around 70% mortality.At the 30th generation,comparison of sensitivity between the selected strains (LOC1 and LOC2) and the original susceptible strain (CA S) indicated a tolerance factor (TF) at the 50% mortality level (LT 50 ) of 4 7 and 3 9 fold,respectively.Throughout the selection process,log time against probit mortality lines remained roughly parallel and the slopes remained lower than that of CA S strain until the last generation.The implication is that at high level of selection,multiple genetic factors continued act together even at the 30th generation to select for adaptation to survival at depleted O 2 concentration.Up to 30th generation,two selected strains still possessed the genetic potential to develop resistance to LOC.Removal of selection pressure for 5 generations from 2 sub populations of two selected strains from 25th generation caused significant reduction in resistance.In the absence of CA exposure,the two selected strains all possessed the reproductive disadvantages or fitness defect.LOC1 and LOC2 were calculated by R 0 to have a fitness value of 0 56 and 0 75 relative to unselected strain,respectively.
基金National Natural Science Foundation of China (62175183)。
文摘Our study investigated the role of oxygen in mediating the FLASH efect.This efect,which was frst reported in vitro in the 1950s and in vivo in the 1970s,recently gained prominence with a number of publications showing diferential sparing between normal tissues and tumors.Oxygen depletion(and subsequent induction of transient hypoxia)is the oldest and most prominent hypothesis to explain this efect.To better understand how the oxygen depletion hypothesis and oxygen enhancement ratio(OER)are relevant for interpreting FLASH benefts,an analytical model was proposed to estimate the sparing factor.The model incorporated factors such as OER,oxygen partial pressure(pO_(2)),loco-regional oxygen difusion/metabolism,total dose and dose rate.The sparing factor,was used to quantify the sparing of normal tissue(initially physoxic).The radiosensitivity parameters of two cell types(V79 Chinese hamster cells and T1 human kidney cells)were selected.Furthermore,the transient behavior of OER during fnite time intervals was modeled,for both without and with the presence of oxygen transport using a difusion model.For tissues with an oxygen consumption rate of 20mmHg/s and a distance of 60μm away from blood vessels,the sparing factor demonstrates an increase from 1.03/1.06(V79/T1)at 2.5Gy/s up to 1.28/1.72(V79/T1)at 100Gy/s(total dose:10Gy).For normal tissues of initial pO_(2) between 1.5 and 8mmHg,the beneft from pushing the dose rate above 100Gy/s is found to be marginal.Preliminary animal experiments have been conducted for validation.Overall,our study predicts that the dose rate associated with maximum normal tissue protection is between 50Gy/s and 100Gy/s.Other than the postulation of the hypoxic stem cell niches in normal tissues,we believe that a framework based upon the oxygen depletion hypothesis and OER is not able to efciently interpret diferential responses between normal and tumor tissue under FLASH irradiation.
文摘FLASH radiotherapy(FLASH-RT)is a new strategy for tumor treatment with an ultra-high dose rate of more than 40 Gy/s.Compared with conventional radiotherapy(CONV-RT),FLASH-RT has no different inhibitory effects on tumors but less damage to normal tissues,which is called the“spare”effect.The“spare”effect triggers our exploration of the great prospect of subverting conventional radiotherapy and its intricate mechanisms.Mitochondrial homeostasis,the immune microenvironment,or DNA integrity may potentially represent the primary breakthrough direction in understanding the mechanisms.Concurrently,it is imperative to advance timely clinical translation efforts.Clinical trials of FLASH-RT have progressed to Phase II in both the United States and Switzerland,with current findings suggesting that FLASH-RT achieves comparable efficacy to CONV-RT while mitigating side effects in select cancer cell types.While summarizing the existing FLASH experiments,this paper emphasizes the significance of clinical transformation and the challenges that will be faced and proposes possible solutions.
