Development of radiation countermeasure agents for acute radiation syndromes

The risk of internal and external exposure to ionizing radiation(IR)has increased alongside the development and implementation of nuclear technology.Therefore,serious security issues have emerged globally,and there has been an increase in the number of studies focusing on radiological prevention and medical countermeasures.Radioprotective drugs are particularly important components of emergency medical preparedness strategies for the clinical management of IR-induced injuries.However,a few drugs have been approved to date to treat such injuries,and the related mechanisms are not entirely understood.Thus,the aim of the present review was to provide a brief overview of the World Health Organization's updated list of essential medicines for 2023 for the proper management of national stockpiles and the treatment of radiological emergencies.This review also discusses the types of radiation-induced health injuries and the related mechanisms,as well as the development of various radioprotective agents,including Chinese herbal medicines,for which significant survival benefits have been demonstrated in animal models of acute radiation syndrome.

Application of Low Tube Voltage, Low-concentration Contrast Agent Using a 320-row CT in Coronary CT Angiography: Evaluation of Image Quality, Radiation Dose and Iodine Intake

The effect of low voltage and low concentration contrast agent on image quality of coronary CT angiography,radiation dose and iodine intake was evaluated.A total of 121 patients with body mass index(BMI)<26 kg/m2 and heart rate(HR)<70 beats/min were randomly divided into four groups:group A(n=31,80 kVp,270 mgl/mL);group B(n=33,100 kVp,270 mgl/mL);group C(h=30,100 kVp,320 mgl/mL);group D(w=27,100 kVp,400 mgl/mL).The automatic current modulation system and the iterative algorithm for reconstruction were adopted in each group.The CT values and SD values of the aortic root(AR),subcutaneous fat,left coronary artery opening(LCA),and right coronary artery opening(RCA)were measured in all groups,the signalto-noise ratio(SNR)and contrast noise ratio(CNR)were calculated,and effective radiation dose and iodine intake were recorded.The subjective assessment for image quality was performed by two physicians using a 4-point scale.The results were compared using the one-way ANOVA and rank sum tests.The image quality of the four groups met the clinical diagnostic requirements.The CT values of AR in groups A,B,C,and D were 537.6±71.4,447.2±81.9,445.2±64.9 and 518.5±94.9 Hu,respectively,with no significant difference between group A and group D,or between group B and group C,while CT values in groups B and C were significantly lower than those in groups A and D(P<0.05).In groups A,B,C,and D,the LCA SNR values were 22.7±9.1,23.3±9.1,23.3±7.7 and 26.6±8.9,and the RCA CNR values were 26.9±9.&28.5±11.4,27.7土&8 and 32」±10.6,respectively.The AR visual scores in groups A,B,C and D were 3.8±0.2,3.9±0.3,3.9±0.3 and 4.0±0.3,respectively.There were no significant differences in SNR,CNR and visual score among the four groups(P>0.05).The radiation doses in groups A,B,C and D were 2.6±1.4,3.6±1.&4.9±3.5 and 4.9±2.8 mSv,respectively.The radiation dose in group A was significantly less than that in the rest three groups(P<0.05).The iodine intakes in groups A,B,C and D were 14.9±1.5,15.0±1.5,17.7±2.0 and 18.1±2.5 g,respectively.There was no significant difference in the intake of iodine between groups C and D,or between groups A and B,while iodine intake in groups A and B were significantly reduced as compared with that in groups C and D(P<0.05).It was concluded that for patients with low BMI and controlled HR,compared to 100 kVp tube voltage combined with multiple concentration contrast agents,80 kVp combined with 270 mgl/mL contrast agent is enough to ensure the quality of the images,and can reduce the radiation dose significantly,while reducing the amount of iodine intake notably,thus reducing the incidence of adverse reaction.

Study of ATP borate ester effects on cell sensitization to radiation emitted by a nuclear reactor

Adenosine triphosphate(ATP)borate ester as a new boron agent for boron neutron capture therapy was tested.It was synthesized via a dehydration reaction induced by heating adenosine triphosphate disodium with boric acid.Next,ATP borate ester pretreatments were assessed to study their effects on cell sensitization from exposure to thermal neutron irradiation emitted by a nuclear reactor.Using cell viability assays(CCK8),survival rates of A549 cells pretreated with or without boroncontaining agents,including ATP borate ester and 4-dihydroxyborylphenylalanine(BPA),were measured.One week after feeding an ATP borate ester solution to tumorbearing nude mice,elemental B content values of tumor muscle and blood were measured using inductively coupled plasma mass spectrometry(ICP-MS).Meanwhile,other tumor tissue samples were placed in a culture medium,subjected to a 3-min neutron irradiation exposure,and then fixed in formalin 24 h later for the terminaldeoxynucleotidyl transferase(TDT)-mediated d UTP nick end labeling(TUNEL)immunohistochemical staining analysis.Results showed that A549 cell irradiation sensitization(irradiation dose of 0.33 Gy)varied with pretreatment.Sensitization values of the ATP borate ester pretreatment group were 1.3–14.1 with boron agent concentrations of 0.3–4.5 mM.Within 1.1–3.4 mM,ATP borate ester showed significantly higher sensitization values than BPA.Meanwhile,TUNEL results demonstrated that apoptosis rates of tumor tissue cells exposed to irradiation after ATP borate ester pretreatment significantly exceeded the corresponding rates for BPA-pretreated cells.In animal experiments,although the distribution ratio of ATP borate ester(tumor tissue/normal muscle,T/N)of 1.2 was not significantly different compared with that of BPA(1.3),the total ATP borate ester concentration in the tumor tissue(0.79±0.05μg/g)significantly exceeded that of BPA(0.58±0.05μg/g).Thus,compared with BPA,the greater enrichment of ATP borate ester in tumor tissues permits preferential targeting toward tumor cells for radiation sensitization.Therefore,ATP borate ester is superior to BPA for use in boron neutron capture therapy.

Colchicine sensitizes human hepatocellular carcinoma cells to damages caused by radiation

AIM： We studied the effect of colchicine combined with radiation on the survival of human hepatocellular carcinoma （HCC） HA22T/VGH cells.METHODS： Twenty-four hours after treatment with 0-8 ng/mL colchicine, HA22T/VGH cells were irradiated at various doses （0, 1, 2, 4, and 8 Gy）. Colony assay was performed to assess the surviving cell fraction. Survival curves were fitted by using a linear-quadratic model to estimate the sensitizer enhancement ratio （SER）. Flow cytometry was used for cell cycle analysis.RESULTS： Colchicine at lower concentrations （1 and 2 ng/mL） had obvious synergy with radiation to inhibit HCC cell growth, whereas higher concentrations （4 and 8 ng/mL） had only additive effect to radiation. Pretreatment with 1 and 2 ng/mL colchicine for 24-h enhanced cell killing by radiation with SERs of 1.21 and 1.53, respectively.G2/N arrest was only observed with higher colchicine doses （8 and 16 ng/mL） after 24-h treatment, this effect was neither seen with lower doses （1, 2, and 4 ng/mL）nor with any dose after only 1 h of treatment.CONCLUSION： Our results suggest that colchicine has potential as an adjunct to radiotherapy for HCC treatment.Lower doses of colchicine possess radiosensitizing effects via some mechanism other than G2/M arrest. Further study is necessary to elucidate the mechanism.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells

Objective To investigate the function of primary cilia in regulating the cellular response to temozolomide(TMZ)and ionizing radiation(IR)in glioblastoma(GBM).Methods GBM cells were treated with TMZ or X-ray/carbon ion.The primary cilia were examined by immunostaining with Arl13 b andγ-tubulin,and the cellular resistance ability was measured by cell viability assay or survival fraction assay.Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride,the autophagy was measured by acridine orange staining assay.The DNA damage repair ability was estimated by the kinetic curve ofγH2 AX foci,and the DNAdependent protein kinase(DNA-PK)activation was detected by immunostaining assay.Results Primary cilia were frequently preserved in GBM,and the induction of ciliogenesis decreased cell proliferation.TMZ and IR promoted ciliogenesis in dose-and time-dependent manners,and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR.The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair.The interference of ciliogenesis reduced DNA-PK activation,and the knockdown of DNA-PK led to cilium formation and elongation.Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Acoustic design sensitivity analysis of structural sound radiation

This paper presents an acoustic design sensitivity(ADS)analysis on sound radiation of structures by using the boundary element method(BEM).We calculated the velocity distribution of the thin plate by analytical method and the surface sound pressure by Rayleigh integral,and expressed the sound radiation power of the structure in a positive definite quadratic form of the Hermitian with an impedance matrix.The ADS analysis of the plate was thus translated into the analysis of structure dynamic sensitivity and ...

Estimation of enhanced low dose rate sensitivity mechanisms using temperature switching irradiation on gate-controlled lateral PNP transistor

The mechanisms occurring when the switched temperature technique is applied,as an accelerated enhanced low dose rate sensitivity(ELDRS)test technique,are investigated in terms of a specially designed gate-controlled lateral PNP transistor(GLPNP)that used to extract the interface traps(Nit)and oxide trapped charges(Not).Electrical characteristics in GLPNP transistors induced by ^(60)Co gamma irradiation are measured in situ as a function of total dose,showing that generation of Nit in the oxide is the primary cause of base current variations for the GLPNP.Based on the analysis of the variations of Nit and Not,with switching the temperature,the properties of accelerated protons release and suppressed protons loss play critical roles in determining the increased Nit formation leading to the base current degradation with dose accumulation.Simultaneously the hydrogen cracking mechanisms responsible for additional protons release are related to the neutralization of Not extending enhanced Nit buildup.In this study the switched temperature irradiation has been employed to conservatively estimate the ELDRS of GLPNP,which provides us with a new insight into the test technique for ELDRS.

A Sensitivity Study of IAP AGCM to Radiation Changes: Climate Simulation of 125kyr and 115kyr before Present

The IAP AGCM was used to simulate the climate of 125kyr and 115kyr before present. We analysed the results and then studied the sensitivity of the model to the changes of radiation distribution induced by orbital parameter changes. The reasonability of the results was also discussed.

Experimental investigation of pre-irradiation effect on radiation sensitivity of temperature sensing fiber Bragg gratings

The effect of pre-irradiation on radiation sensitivity of fiber Bragg gratings （FBGs） is verified experimentally. FBGs are fabricated in photosensitive optical fibers and single mode fibers with Ce-concentration in a range from 3 mol% to 23.37 mol% in the core. In experiments, the FBGs are subjected to twice v-radiation exposures to a Co^60 source at a dose-rate of 0.1 Gy/s up to a total dose of 50 kGy. Pre-irradiation treatment can reduce the temperature sensitivity variation of FBGs by 18.12%-35.91%, as well as Bragg wavelength shift （BWS） by 8%-27.08 %. Our research demonstrates that pre-irradiation treatment is a feasible method to improve the radiation tolerance of FBGs.

Apoptotic Sensitivity to Irradiation Increased after Transfection of chk1 Antisense Chain to HL-60 Cell Line

Summary： The HL-60 cells were transfected with chkl antisense and sense chain, and 24 h later subjected to irradiation. Twenty-four h after irradiation, the changes in the chk1 protein expression was assayed by Western blot, and the cell cycles and apoptosis rate detected by FCM. The irradiated apoptosis sensitivity was increased by antisense blocking of chk1 gene in HL-60 cell line with the apoptosis rate being 26.31 %, significantly higher than that by the sense blocking （10.34 %, 0. 025〈P〈0.05）. In HL-60 cells transfected with chkl antisense chain, the G2/M phase arrest was attenua：ted and the cells in G2/M phase were accounted for 38.42 %, significantly lower than those of the cells transfected with chkl sense chain （54.64 %, 0. 005〈P〈0.01）. It was concluded that antisense blocking of chk1 gene could increase the apoptosis sensitivity to irradiation.

Remarkably different results between two studies from North America on genomic mutations and sensitivity to DNA demethylating agents for myelodysplastic syndromes

Sekeres et al. （1） conducted a multicenter randomized, controlled trial to compare whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates to azacitidine in the treatment of myelodysplastic syndromes （MDS）. In that trial, 224 patients with higher-risk MDS and 53 with chronic myelomonocytic leukemia （CMML） were enrolled and randomly assigned to the ＂azacitidine＂ group, ＂azacitidine plus lenalidomide＂ group or ＂azacitidine plus vorinostat＂ group. The researchers found that patients with MDS treated with azacitidine-based combinations had similar response rate to azacitidine monotherapy. Using genomic mutation analysis, they found that the overall response rate to azacitidine-based treatment was higher for patients with mutations in DNMT3A and lower for those with mutations in SRSF2. Whereas in another study, Welch et al. enrolled 26 patients with MDS and 90 with acute myeloid leukemia （AML） who were treated with decitabine, and they found that patients with TP53 mutations had a higher response rate, but not those with DNMT3A mutations （2）. We propose that this big discrepancy in the conclusions between the two studies might have been caused by the presence of many co-interacting factors, e.g. study aims, DNA demethylating agents, treatment protocols, and patient sources.

A STUDY ON RADIATION CROSSLINKING OF POLYDIMETHYLSILOXANE (PDMS) RUBBER LATEX

Polydimethylsiloxane (PDMS) rubber latex with two sorts of sensitizers, trimethylol propane tri-methacrylate (TMPTMA) and diethylene glycol di-acrylate (DEGDA), was irradiated with γ-rays and electron beams in various conditions. The radiation crosslinking reaction of PDMS occurs in the inner phase of the latex and is relatively isolated from the water phase. Therefore the oxygen and the radicals produced by the radiolysis reaction of water almost have no effect on the crosslinking reaction of polymer. The experimental data correspond with the Charlesby-Pinner relationship in the main. The gelation doses, degree of crosslinking and degradation as well as G values of crosslinking were calculated. From them, the sensitization coefficients were derived to offer a quantitative measurement of the enhancing effect of sensitizer on the radiation crosslinking.

Parameterizations of Surface Radiation in the Semiarid Grasslands of Inner Mongolia under Clear-Sky Conditions Using MODIS Data

A set of improved and efficient radiation parameterization schemes for surface radiation balance components under clear- sky conditions was developed by using general surface measurements and MODIS data. The set of schemes was then adapted for regions similar to the present study sites under different grazing intensities and varying degrees of drought in the semiarid grasslands of Inner Mongolia. Specifically, we mainly improved two schemes for estimating downward shortwave and longwave radiation at the surface, which could be applied to regions with certain degrees of drought. The validation datasets were from ground-based observations at various grazing sites during the growing season （May to September） of different drought years, 2005 and 2006. Through comparisons of parameterized versus measured radiation values, the increased or modified factors in the original schemes demonstrated improved estimation accuracy, and the rationalities of input parameters and variables were analyzed. The regional instantaneous net radiation estimations had root-mean-square errors of less than 30 W m-2 compared with ground measurements at the sites during the study period. The statistical results showed the improved schemes are suitable for estimating surface net radiation in regional semiarid areas during the growing season. Analyses of the sensitivity of the schemes to corresponding variables were conducted to ascertain the major error sources of the schemes and potential variables for improving the performance of the schemes in agreement with observations.

Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy

Microvessels promote proliferation of tumor cells by delivering oxygen and nutrients, but rapid growth of tumors results in unmet demands for oxygen and nutrients, thereby creating a hypoxia microenvironment. Under hypoxic conditions, vascular endothelial cells（ECs） initiate the formation of immature and abnormal microvasculature. This results in leakage and tortuosity that facilitates tumor cell invasion, metastasis and resistance to cytotoxic treatment.Radiotherapy（RT） is a vital tumor treatment modality. Currently, more than 60% of patients with malignant tumors receive RT at certain points during their treatment. Hypoxia induced by abnormal microvessels can hamper the cytotoxic effect of ionizing radiation, particularly, stereotactic body radiotherapy（SBRT）. Anti-angiogenesis（AA） agents are known to reduce and renormalize microvessels in tumors, and hence alleviate hypoxia. The combination of AA agents with SBRT may have a synergistic role in inhibiting the growth of tumors. On the contrary, large doses of irradiation may affect tumor microvessels itself. In this review, we aim to clarify the relationship between SBRT and microvessel formation in tumors. In addition, we provide a retrospective analysis of the combination therapy involving SBRT and AA agents in preclinical and clinical practice to define its role in antitumor treatment.

Observations and Modeling of Incoming Longwave Radiation to Snow Beneath Forest Canopies in the West Tianshan Mountains, China

Forest canopy reduces shortwave radiation and increases the incoming longwave radiation to snowpacks beneath forest canopies. Furthermore, the effect of forest canopy may be changed by complex topography. In this paper, we measured and simulated the incoming longwave radiation to snow beneath forest at different canopy openness in the west Tianshan Mountains, China(43°16'N, 84°24'E) during spring 2013. A sensitivity study was conducted to explore the way that terrain influenced the incoming longwave radiation to snow beneath forest canopies. In the simulation model, measurement datasets, including air temperature, incoming shortwave radiation above canopy, and longwave radiation enhanced by adjacent terrain, were applied to calculate the incoming longwave radiation to snow beneath forest canopy. The simulation results were consistent with the measurements on hourly scale and daily scale. The effect of longwave radiation enhanced by terrain was important than that of shortwave radiation above forest canopy with different openness except the 20% canopy openness. The longwave radiation enhanced due to adjacent terrain increases with the slope increase and temperature rise. When air temperature(or slope) is relatively low, thelongwave radiation enhanced by adjacent terrain is not sensitive to slope(or air temperature), but the sensitivity increases with the decrease of snow cover area on sunny slope. The effect of longwave radiation is especially sensitive when the snow cover on sunny slope melts completely. The effect of incoming shortwave radiation reflected by adjacent terrain on incoming longwave radiation to snow beneath forest canopies is more slight than that of the enhanced longwave radiation.

Synchrotrons radiation stability measurement and improvement

In the 3rd generation synchrotron light source,beside the orbit,air disturbance and ground vibration also could affect the position stability of photon beam in synchrotrons radiation measurement.In the condition of implementation of orbit feedback system at SSRF,the measured position stability of photon beam in synchrotrons radiation measurement station was presented in this paper.And then the improvement methods of position stability of photon beam were discussed.Finally the measured result was shown when the designed feedback system is implemented to improve the position stability of photon beam.

2-Steps Preparation Activated Carbon from Solidago Canadensis:Carbonized by Electrial heating and Activated by Microwave Radiation

The activated carbon(AC)was prepared from Solidago Canadensis(SC),an alien invasive plant.The plant was firstly carbonized under nitrogen at 400 ℃ for 90 min in an electrical furnace,and then the carbonized product was activated with KOH through microwave radiation.Effects of KOH/C ratio,microwave power,microwave radiation time on the adsorption capacities and yield of AC were evaluated.It indicated that the optimum conditions were KOH/C ratio 2 g/g,microwave power 700 W,and microwave radiation time 6 min.The carbonation process of SC was analyzed by thermogravimetry(TG).The pore structural parameters and surface functional groups of the AC were characterized by nitrogen adsorption-desorption and Fourier Transformed Infrared Spectroscopy(FTIR),respectively.The activation yield,the surface area,the average pore size,and the average micropore size of AC prepared from optimum conditions were 53.75%,1 888 m2/g,0.567 nm,and 0.488 nm,respectively.The adsorption amounts of AC were 302.4 mg/g for methylene blue and 1 470.27 mg/g for iodine.

Thermo-sensitive polymer nanospheres as a smart plugging agent for shale gas drilling operations

Emulsifier-free poly（methyl methacrylate-styrene） [P（MMA-St）] nanospheres with an average particle size of 100 nm were synthesized in an isopropyl alcoholwater medium by a solvothermal method. Then, through radical graft copolymerization of thermo-sensitive mono- mer N-isopropylacrylamide （NIPAm） and hydrophilic monomer acrylic acid （AA） onto the surface of P（MMA- St） nanospheres at 80 ℃, a series of thermo-sensitive polymer nanospheres, named SD-SEAL with different lower critical solution temperatures （LCST）, were prepared by adjusting the mole ratio of NIPAm to AA. The products were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, particle size distribution, and specific surface area analysis. The temperature-sensitive behavior was studied by light transmittance tests, while the sealing performance was investigated by pressure transmission tests with Lungmachi Formation shales. The experimental results showed that the synthesized nanoparticles are sensitive to temperature and had apparent LCST values which increased with an increase in hydrophilic monomer AA. When the temperature was higher than its LCST value, SD- SEAL played a dual role of physical plugging and chemical inhibition, slowed down pressure transmission, and reduced shale permeability remarkably. The plugged layer of shale was changed to being hydrophobic, which greatly improved the shale stability

Synthesis and properties of p(NIPA-co-NVP)/clay hydrogels by radiation polymerization

In this study,hydrogels of P(NIPA-co-NVP)/clay were synthesized byγ-ray radiation.Different thermo-sensitive hydrogels were made under different experimental conditions such as dose,monomer ratio,and con- tent of clay.X-ray diffraction shows that the layer distance between Na-clays is changed from 1.6 to 2.7 nm because Na-clay pieces can be intercalated or exfoliated by HTMAB,and that between P(NIPA-co-NVP)/clay pieces is 3.4 nm. The swelling property tests show that the LCST of P(NIPA-co-NVP) is higher than PNIPA.With the increase of NVP content,LCST is higher.As the ratio of NIPA/NVP is 95/5,hydrogel shows the best swelling property and LCST is 37℃.LCST of P(NIPA-co-NVP)/clay hydrogel is not changed,but the strength and swelling properties are better.