Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

BACKGROUND:As a common disease in middle-aged and elderly,osteoarthritis is difficult to cure,and the pathogenesis is not clear.Long non-coding RNA participates in the pathogenesis of osteoarthritis through many ways,such as regulating translation,promoting or inhibiting mRNA,and adsorbing miRNAs. OBJECTIVE:To review the types of common long non-coding RNA in osteoarthritis,and the influence of multiple long non-coding RNAs on the pathological factors related to osteoarthritis,to analyze the future application of long non-coding RNAs in osteoarthritis. METHODS:Literature retrieval was conducted in CNKI,WanFang Data,VIP database,PubMed,Web of Science and Sciencedirect databases,using the search terms of"osteoarthritis,degenerative joint disease,degenerative arthritis,OA,LncRNA,long non-coding RNA,long noncoding RNA,long intergenic non-coding RNA"in Chinese and English.All relevant literature published from 1976 and May 2024 was retrieved.After literature screening,induction,analysis and summary,93 articles were finally included for review. RESULTS AND CONCLUSION:This review collected 25 long non-coding RNAs that are well studied with osteoarthritis.Long non-coding RNAs,as a molecular sponge for miRNA,are competing endogenous RNAs to competitively adsorb miRNAs and then affect downstream targets.Long non-coding RNAs can regulate physiopathological processes such as chondrocyte apoptosis and proliferation,cartilage extracellular matrix degradation,and inflammatory responses.Long non-coding RNAs are expected to become a biomarker and potential therapeutic target for the clinical diagnosis and therapeutic prognosis of osteoarthritis,and it may become a new strategy for the clinical treatment of osteoarthritis in the future.

ObjectiveTo evaluate the clinical efficacy and safety of Tripterygium wilfordii polyglycoside tablets （TWP） in the treatment of rheumatoid arthritis （RA） in the real world. MethodDiagnosis and treatment data of patients with RA in Chinese medicine rheumatology registration research information platform information database （CERTAIN） from January 1，2019 to January， 2024 were collected. According to the inclusion and exclusion criteria， data were screened. The included data were divided into an exposure group and a control group according to the use of TWP or not. Propensity score matching （PSM） was used in both groups to keep the baseline balanced and comparable. The disease activity score （DAS28-ESR） of 28 joints based on the erythrocyte sedimentation rate （ESR）before and after treatment was compared between the two groups， as well as health assessment questionnaire （HAQ），visual analogue scale （VAS），tender joint count （TJC），swollen joint count （SJC）， patient's global assessment （PGA），evaluator's global assessment （EGA），laboratory indexes， clinical curative effect， and adverse reactions. ResultA total of 3 978 patients were included，including 929 in the exposure group and 3 049 in the control group. Before PSM，there were significant differences in demographic information，DAS28-ESR score，PGA，EGA，HAQ，VAS scores，SJC， and TJC between the two groups （P<0.05）. After successful PSM matching，922 patients in the exposure group and 922 patients in the control group were included. There was no significant difference in demographic information and DAS28-ESR between the two groups before treatment，and the differences in other indexes between the two groups decreased to varying degrees. After treatment，the DAS28-ESR，PGA，EGA，HAQ，SJC，TJC，VAS scores， ESR，and IgG immune index of the two groups were significantly lower （P<0.01）. Compared with those in the control group after treatment，the DAS28-ESR，PGA，EGA，HAQ，VAS scores， and ESR in the exposure group after treatment decreased more significantly （P<0.05，P<0.01）. There was no significant difference in TJC in the exposure group after treatment. However， TJC in the exposure group was significantly higher than that in the control group before treatment （P<0.05）. In terms of TJC reduction，the exposure group performed better than the control group. There was no significant difference in SJC and IgG between the exposure group and the control group after treatment. After treatment，the clinical symptoms of poor appetite，insomnia and many dreams，upset，fatigue，and fear of wind and cold in the two groups were improved. Except that the proportion of women in the exposure group was higher than that in the control group （P<0.01），there was no significant difference in the incidence of other adverse reactions between the two groups after treatment. ConclusionTWP to treat RA can effectively reduce DAS28-ESR，PGA，EGA，HAQ，TJC，and VAS scores and improve the general symptoms. Except for the women at childbearing age with fertility requirements that TWP is not applicable，it shows good security.

Working memory is a core component of human cognitive functions, responsible for the temporary storage and manipulation of information, and plays a vital role in the execution of daily tasks. Working memory includes information encoding, maintenance, manipulation, and retrieval, with the underlying mechanisms corresponding to neural oscillations. The frequency bands most related to each step of working memory are θ (4-8 Hz), α (8-13 Hz), and γ (>30 Hz) waves. θ waves mainly correspond to the temporal organization of memory items; γ waves are related to information maintenance; α waves indicate inhibition of irrelevant information. These neural oscillations can be regulated by external rhythmic stimulation, gradually synchronizing to the rhythm and phase of external stimulation. This phenomenon is called neural entrainment. Non-invasive brain stimulation (NIBS) can regulate working memory related neural oscillations through entrainment, and has the potential to become a method to enhance working memory performance. Another possible intervention approach to improve working memory is to enhance the excitability of key brain regions involved in working memory through NIBS. In this review, we reviewed more than 50 studies applying NIBS for working memory in healthy adults, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and other NIBS techniques. In terms of research paradigm, working memory NIBS studies with healthy adults usually adopt classic working memory behavioral paradigms, e.g., n-back tasks with numbers or space positions, Sternberg tasks, relatively few stimulating sessions, mainly focus on the simultaneous or short-term effects on behavioral performance. For stimulation sites, the prefrontal cortex (especially dorsolateral prefrontal cortex (DLPFC) is the most commonly choice for it’s a vital role in functions such as information maintenance and cognitive resource allocation. The parietal lobe (especially the intraparietal sulcus (IPS) also plays an important role in information maintenance and manipulation, and is the second common stimulation site after DLPFC. Studies targeting the temporal lobe, occipital lobe, and motor cortex are relatively limited. For stimulation methods, TMS studies mainly use repetitive TMS (rTMS) and θ burst stimulation (TBS) with stimulating frequency in θ or γ band, one-sided or bilateral prefrontal cortex as the stimulation site. The specific intervention effects may also depend on the phase of the neural oscillation that TMS targets. For tDCS studies, anodal stimulation of DLPFC or parietal lobe is widely utilized. The heterogeneous intervention effects such as relatively weak enhancement or impairment of working memory performance after intervention, may result from varied stimulation protocol or participants’ factors (e.g., small sample size, inconsistent baseline levels). For tACS studies, the most widely used stimulation frequencies are θ and γ bands, usually with in-phase manner, fixed or individualized frequencies. Enhancement of working memory performance has been reported for both settings, and the effects are also affected by stimulation parameters, task difficulty and baseline levels of participants. Transcranial random noise stimulation (tRNS), temporal interference stimulation (TIS), transcranial ultrasound stimulation (TUS) are emerging NIBS techniques, of which TIS and TUS can stimulate deep brain regions. Current studies modulating working memory based on these cutting-edge techniques are limited, but they have potential in mechanism exploration and clinical applications in working memory research.

Objective:To investigate the prevalence of adult skeletal fluorosis caused by drinking tea-type endemic fluorosis in Yushu Tibetan Autonomous Prefecture (hereinafter referred to as Yushu Prefecture), Qinghai Province, and provide scientific basis for prevention and control of the disease.Methods:In August 2021, one village was selected as a survey site in six counties (cities) in Yushu Prefecture, including Nangqian, Chindu, Yushu, Zadoi, Qumarlêb, and Zhiduo. Drinking water samples and 10 brick tea samples were collected from each village to determine the fluoride content in water and brick tea; at least 100 permanent residents aged ≥ 25, who had a habit of drinking brick tea and had lived in the local area for more than 5 years, were selected for X-ray imaging to examine the prevalence of adult skeletal fluorosis.Results:A total of 75 samples of residential drinking water were collected, with a fluoride content of (0.21 ± 0.05) mg/L, ranging from 0.11 to 0.34 mg/L; 60 samples of brick tea, with a fluoride content of (626.70 ± 157.27) mg/kg, ranging from 324.00 to 2 102.00 mg/kg. A total of 1 136 adults were examined, and 318 cases of skeletal fluorosis were diagnosed, with a detection rate of 27.99%. Among them, the detection rates of mild, moderate, and severe skeletal fluorosis were 20.95% (238/1 136), 6.07% (69/1 136), and 0.97% (11/1 136), respectively, with mild symptoms being the main. The detection rates of skeletal fluorosis in males and females were 29.09% (121/416) and 27.36% (197/720), respectively, with no statistically significant difference between the gender (χ 2 = 0.39, P = 0.533). Comparison of the skeletal fluorosis in different gender, the differences were statistically significant (χ 2 = 22.31, P < 0.001). The detection rates of skeletal fluorosis in the age groups of 25 - 35, 36 - 45, 46 - 55, 56 - 65, 66 - 75, and ≥76 years old were 6.86% (7/102), 22.37% (51/228), 24.02% (92/383), 37.44% (73/195), 43.48% (70/161), and 37.31% (25/67), respectively. The differences between the groups were statistically significant (χ 2 = 59.84, P < 0.001). Moreover, there was a statistically significant difference in the composition of skeletal fluorosis among different age groups ( H = 37.66, P < 0.001). The Spearman correlation analysis results showed that the severity of adult skeletal fluorosis was positively correlated with age ( r = 0.34, P < 0.001). Conclusions:There is a certain degree of prevalence of adult skeletal fluorosis in Yushu Prefecture. And as age increases, the condition of skeletal fluorosis becomes more severe.

Objective To investigate the effect of Ophiopogonin D on lipopolysaccharide(LPS)-induced apoptosis of alveolar epithelial cells by regulating the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A549 AT Ⅱ cells cultured in vitro were randomly divided into four groups:control group,LPS group,LPS+Ophiopogonin D group,LPS+Ophiopogonin D+colivelin(JAK2/STAT3 signal activator)group,except for the control group,and cells in all other groups were established injury models while being grouped with Ophiopogonin D and colivelin for treatment.Cell counting kit-8(CCK-8)experiment and flow cytometry were applied to detect cell proliferation and apoptosis in each group;Western blotting was applied to detect the expression of IL-6/JAK2/STAT3 signaling pathway proteins of cells in each group.Results The apoptosis rates of A549 cells in control group,LPS group,LPS+Ophiopogonin D group and LPS+Ophiopogonin D+colivelin group were(2.52±0.73)％,(52.43±4.14)％,(1.67±0.52)％and(47.94±3.43)％;IL-6 protein levels were 0.14±0.03,0.49±0.05,0.17±0.04 and 0.45±0.06,and p-JAK2/JAK2 protein levels were 0.17±0.04,0.64±0.08,0.19±0.06 and 0.61±0.07;p-STAT3/STAT3 protein levels were 0.20±0.06,0.69±0.10,0.22±0.07 and 0.65±0.09;the apoptosis rates of AT Ⅱ cells were(3.01±0.69)％,(55.16±3.94)％,(2.35±0.71)％and(50.28±3.78)％;the levels of IL-6 protein were 0.11±0.03,0.87±0.13,0.19±0.04 and 0.84±0.12;the p-JAK2/JAK2 protein levels were 0.13±0.04,0.56±0.08,0.15±0.03 and 0.53±0.07;p-STAT3/STAT3 protein levels were 0.30±0.08,0.79±0.14,0.33±0.09 and 0.75±0.13.The above indexes:control group,LPS+Ophiopogonin D group compared with LPS group,LPS+Ophiopogonin D+colivelin group compared with LPS+Ophiopogonin D group,the differences were statistically significant(all P＜0.05).Conclusion Ophiopogonin D can reduce LPS induced inflammation and oxidative stress levels by inhibiting the activation of IL-6/JAK2/STAT3 signaling pathway,ultimately reducing LPS-induced apoptosis of alveolar epithelial cells.

Objective:To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou(CHERRY)study.Methods:A decision-analytic Markov model was used to simulate and compare different antihy-pertensive initiation strategies,including:Strategy 1,initiation of antihypertensive therapy for Chinese adults with systolic blood pressure(SBP)≥140 mmHg(2020 Chinese guideline on the primary preven-tion of cardiovascular diseases);Strategy 2,initiation of antihypertensive therapy for Chinese adults with SBP≥130 mmHg;Strategy 3,initiation of antihypertensive therapy for Chinese adults with SBP ≥140 mmHg,or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases(2017 American College of Cardiology/American Heart Association guideline for the prevention,detection,evaluation,and management of high blood pressure in adults);Strategy 4,initiation of antihypertensive therapy for Chinese adults with SBP≥ 160 mmHg,or with SBP between 140 and 160 mmHg and at high risk of car-diovascular diseases(2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults:Diagnosis and management).The high 10-year cardiovascular risk was de-fined as the predicted risk over 10％based on the 2019 World Health Organization cardiovascular disease risk charts.Different strategies were simulated by the Markov model for ten years(cycles),with parame-ters mainly from the CHERRY study or published literature.After ten cycles of simulation,the numbers of quality-adjusted life years(QALY),cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy,and the numbers needed to treat(NNT)for each cardiovas-cular event or all-cause death could be prevented were calculated to assess the intervention efficiency.One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilis-tic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.Results:A to-tal of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included.Com-pared with strategy 1,the number of cardiovascular events that could be prevented in strategy 2 increased by 666(95％UI:334-975),while the NNT per cardiovascular event prevented increased by 10(95％UI:7-20).In contrast to strategy 1,the number of cardiovascular events that could be prevented in strategy 3 increased by 388(95％UI:194-569),and the NNT per cardiovascular event prevented decreased by 6(95％UI:4-12),suggesting that strategy 3 had better health benefits and intervention efficiency.Compared to strategy 1,although the number of cardiovascular events that could be prevented decreased by 193(95％UI:98-281)in strategy 4,the NNT per cardiovascular event prevented decreased by 18(95％UI:13-37)with better efficiency.The results were consistent in the sensitivity analyses.Conclusion:When initiating antihypertensive therapy in an economically developed area of China,the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold.The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.

Objective:Survival analysis of cancers' incidence data in Tianjin from 2010 to 2016 was conducted to provide the basis for formulating and evaluating regional health policies on cancer prevention and treatment.Methods:Registration data in Tianjin were used between January 1, 2010 to December 31, 2016 and patients were followed-up till 31 December, 2021. Life-table method was used to calculate the observed survival rate and Edered Ⅱ was used to calculate the relative survival rate. The data were stratified by year, gender, age group and cancer sites. Difference in survival curves between group was analyzed by Kaplan-Meier method and Log rank test. Joinpoint regression model was used to analyze the trend change.Results:The 5-year relative survival rates of cancer were 41.92% to 53.65% from 2010 to 2016 for residents in Tianjin, with an increasing trend ( t=4.81 ,P=0.005), and the average was 48.56%. The survival rate of females was higher than that of males (57.71%vs. 39.20%), and the survival rate of urban residents was higher than that of rural residents (49.38% vs. 47.24%). The 5-year relative survival rates were 63.14%, 78.39%, 58.25% and 32.67% in 0-14, 15-44, 45-64 and 65 and above age groups, respectively. The median relative survival times of all cancer were 2.34 to 6.00 years from 2010 to 2016 in Tianjin, with an increasing trend ( t=3.86, P=0.012). The average of median relative survival times was 4.11 years. The median survival time of females was longer than that of males (11.99 years vs. 2.03 years), and the time of urban residents were longer than that of rural residents (4.60 years vs. 3.43 years). The median relative survival time were 12.07, 11.92 and 1.34 years in 15-44, 45-64 and 65 and above age groups, respectively. Conclusions:The cumulative survival rate of cancer increased significantly from 2010 to 2016 in Tianjin, indicating that the prevention and treatment effect of cancer is obvious. The focus should be on male, rural areas, higher age group, and targeted prevention and treatment measures should be taken to lung, esophagus, liver, gallbladder and pancreatic cancer.

Objective:To explore the trends and distribution of liver cancer between sexes, ages, and urban-rural areas in Tianjin, China from 1999 to 2021, and provide data for targeted prevention and control strategies of liver cancer in Tianjin.Methods:Liver cancer mortality data of Tianjin during 1999-2021 were from the Tianjin population based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC), and the population data of permanent Tianjin residents were from Tianjin Municipal Public Security Bureau. Liver cancer mortality, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALY) were calculated using the cause of death surveillance data collected by Tianjin Centers for Disease Control and Prevention. The distributions of these data among residents of different sexes, ages, and regions were analyzed. Segi's world standard population was used for standardization. Joinpoint regression was used for trend analysis on the mortality rate of liver cancer and the disease burden.Results:The liver cancer mortality rate in Tianjin decreased by 46.75% from 1999 to 2021, with distinct phased characteristics. From 1999 to 2010, the age-sex-standardized mortality rate (SMR) decreased from 12.62/100 000 to 11.64/100 000 with an annual percent change (APC) of -1.32% ( P=0.003). From 2010 to 2021, the SMR decreased from 11.64/100 000 to 6.72/100 000 (APC=-3.89%, P＜0.001). The age-sex-standardized DALY rates(SDR) decreased by 50.63% from 1999 to 2021, also with distinct phased characteristics. From 1999 to 2010, the SDR decreased from 388.67/100 000 to 349.38/100 000 (APC=-1.35%, P=0.002). From 2010 to 2021, the SDR decreased from 349.38/100 000 to 191.88/100 000 (APC=-4.43%, P＜0.001). The liver cancer mortality rate declined most rapidly in the age group under 45 years; the APC for those under 35 years was -5.07% ( P＜0.001), and for those aged 35-44 years, the APC was 0.63% ( P=0.707) and -8.21% ( P＜0.001) before and after 2007, respectively. Both SMR and SDR were significantly higher in males than in females ( P＜0.01). Both SMR and SDR were significantly higher in urban areas than in rural areas from 1999 to 2007 ( P＜0.05), but they became similar after 2008. Liver cancer DALY are predominantly YLL, accounting for 99%. The median age of liver cancer deaths in Tianjin during 1999-2021 was 64-68 years old, with males lower than females ( P＜0.05), and rural areas lower than urban areas ( P＜0.05), generally showing an increasing trend (1999-2014: APC=0.11%, P=0.047; 2014-2021: APC=0.51%, P=0.005). Conclusions:Liver cancer mortality rate and disease burden decreased from 1999 to 2021 in Tianjin, with an especially accelerated decline after 2010. Further efforts to reduce liver cancer mortality in Tianjin are needed, and special attention should be focused on the elderly, male, and rural residents.

Objective To investigate the protective effect and mechanism of CDK4/6 inhibitor palbociclib against radiation-induced injury in rats'small intestinal crypt epithelial cell line(IEC-6).Methods(1)Using CCK-8 colorimetric assay,colony formation assay,the PI staining method,Annexin V-FITC/PI dual staining and Western blot,the impact of palbociclib on proliferation,cell cycle dynamics,apoptosis,DNA damage,as well as phosphorylation events at Rb-780 and 795 sites in irradiated IEC-6 cells was investigated.(2)An IEC-6 cell line overexpressing Rb was established,and the effects of Rb overexpression on proliferation,cell cycle,and apoptosis in the IEC-6 cell line were assessed using the CCK-8 colorimetric assay,PI staining method,Annexin V-PE/7-AAD dual staining and Western blot.Additionally,the impact of Rb overexpression on the protective effect of palbociclib against radiation damage was verified in the Rb-overexpressing IEC-6 cell line.Results(1)Administration of palbociclib was demonstrated to enhance the proliferative capacity of IEC-6 cells following exposure to 10 Gy X-ray irradiation,increase colony formation ability post 4-8 Gy X-ray exposure while concomitantly reducing the proportion of cells in the G2/M phase after 10 Gy irradiation and diminishing apoptosis in irradiated IEC-6 cells.Protein expression analysis revealed that palbociclib inhibited phosphorylation at Rb-780 and 795 sites and attenuated the production of γ-H2AX in IEC-6 cells following irradiation.(2)After transfection of IEC-6 cells with Rb overexpression lentivirus,there was a significant increase in the total protein expression of Rb.The phosphorylation levels at Rb-780 and 795 sites were markedly elevated.Consequently,cell proliferation was accelerated,the proportion of cells in the S phase of the cell cycle increased,and the apoptotic rate significantly rose after exposure to 10 Gy X-ray irradiation.(3)Treatment with a lower dose of palbociclib(0.05 μmol/L)was found to suppress the phosphorylation of Rb at 780 and 795 sites in IEC-6 cells overexpressing Rb.Additionally,it reduced apoptosis in IEC-6 cells overexpressing Rb following exposure to 10 Gy X-ray irradiation.However,this treatment did not inhibit the phosphorylation of Rb at 780 and 795 sites in IEC-6 cells transfected with the empty vector,nor did it exert a protective effect against radiation-induced damage in these cells.Conclusion The CDK4/6 inhibitor palbociclib demonstrates significant protective effects against radiation-induced damage in rats'intestinal crypt epithelial cell line(IEC-6),with the Rb protein potentially playing a crucial role in mediating this radioprotective response.