Objective To prepare 2-[18F]fiuoropropionic acid (18F-FPA) and evaluate its biodistribution and imaging capacity in Lewis lung carcinoma-bearing mice.Methods 18F-FPA was prepared by nucleophilic substitution reaction,and its hydrophilicity was analyzed.18F-FPA (7.4-11.1 MBq) was injected into Lewis lung carcinoma-bearing mice via tail vein.MicroPET imaging was performed at 20,80 min after the injection.The biodistribution of 18F-FPA in organs was analyzed.The blocking effects of sodium propionate and dichloroacetate to 18F-FPA were tested in vivo.Data were analyzed by two-sample t test using GraphPad Prism software.Results The synthesis of 18F-FPA took 40 min.18F-FPA had high radiochemical purity (＞99％) and hydrophilicity.18F-FPA was mainly distributed in the carcinoma,the urinary bladder and the caecum.The radioactive uptakes in muscles,brown fat and bones were relatively low.Quantitative analysis showed that the uptake of 18F-FPA in Lewis lung carcinoma from 20 min to 80 min was slightly increased ((17.03±2.87) ％ID/g vs (19.33±2.45) ％ID/g) without significant difference (t=1.100,P＞0.05).Neither sodium propionate nor dichloroacetate could block the uptake of 18F-FPA in Lewis lung carcinoma (t=1.544,0.894;both P＞0.05).Conclusions 18F-FPA can be quickly synthesized and has good physicochemical properties.It can be used as a tracer to visualize Lewis lung carcinoma in mice,and its tumor uptaking can not be blocked by propionate and dichloacetate.18 F-FPA PET has the potential to detect lung cancer noninvasively in clinic.

Objective:To investigate the intervention effect of total glucosides of Acanthopanax giraldii Harms(TGA) on learning and memory impairment and the mechanism in cerebral ischemic rats.Methods:The model of transient cerebral ischemic /reperfusion was made by bilateral occlusion of common carotid arteries in rats.Learning-memory ability was observed and the activities of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in brain tissue were measured in rats.Results:In Ymaze test the correct reaction frequency of model group was lower than normal group(P

Objective To study mutagenic effects of spaceflight on physiological and biochemical parameters of Rhodobacter sphaeroides and select high-yield mutants in co-enzyme Q10(CoQ10) production for providing the experimental and theoretical basis for industrial production through mutagenic effects of spaceflight.Methods Variations in stress resistance and CoQ10 production of isolated strains were studied,the strain Rhodobacter sphaeroides was taken back by a recoverable satellite after 15 d flight in space.Results Compared to the control,the strain was characterized by highter NaCl tolerance and higher stress resistance,as well as with broader scope in growth temperature and pH value after spaceflight.The mutant colonies appeared white or pink which was different from their original red.The CoQ10 production of mutant 10 strain was increased by 73.13% much higher than that of control.Conclusion Spaceflight mutagenic effects on Rhodobacter sphaeroides shows to be multi-factor compared to the traditional single-factor mutagenesis methods.It can enhance stress resistance and increase CoQ10 production of isolated strains,and can be utilized in industrial microbial mutagenesis and breeding in the future.

In order to obtain the bifunctional chimeric molecule of single-chain urokinase-type plasminogen activator (scu-PA) which can inhibit platelet aggregation, PRGDWR peptide was inserted into the site between Gly 118 and Leu119 (called insertion mutant B, InB). The recombinant gene of InB was expressed by Pichia pastoris. The secreted protein was purified by metal chelate affinity and strong cation exchange chromatography. The amidolytic ability of mutant InB is 5 900 IU/mg, the kinetic constants is: KInB m,plg=56.8 μmol*L-1，kInBcat,plg=0.33 s- 1. The kinetic constants of plasminogen activation reaction is: KInB m,plg=0.397 μmol*L-1，kInBcat,plg=0.0164 s-1. Fibrin inhibit the catalytiv ability of InB during plasminogen activatio n, the influence factor is 0.463(means InB remain 46.3% of the catalytic abili ty when fibrin was involved in the reaction system). The mutant not only has alm ost the same catalytic ability as wild type scu-PA, but also has strong ability of anti-platelet aggregation(compared with scu-PA), IC50 of InB is 12.7 μmol*L-1.

Because the influence of fibrin on the reaction of plasm inogen activation by various plasminogen activators is different, the kinetic co nstant of the reaction of plasminogen activation catalyzed by InB with and witho ut fibrin were detected. The result is: Kfibrinm＝4.2 μmol*L -1，greater than the normal Km=0.379 μmol*L-1; kfib rincat＝0.107 s-1，greater than the normal kcat=0.0165 s-1. The results suggest that existence of fibrin in the reaction system of plasminogen activation depress the affinity between InB and plasminog en, but accelerates the hydrolysis of plasminogen by InB. The count up effect is inhibition.

Objective To explore the influence of TAC protocol (pirarubicin,cyclophosphamide and docetaxel) and AC-T protocol (pirarubicin,cyclophosphamide and sequential docetaxel) on T lymphocytes cell subsets (included CD3+ T cells,CD3+ CD4+ T cells,CD3+ CD8+ T cells,CD3+ CD4+/CD3 + CD8+),natural killer (NK) cells and part of the quality of life in the peripheral blood of patients.Methods A total of 66 patients with breast cancer included 31 cases for TAC protocol (6 cycles of chemotherapy) and 35 cases for AC-T protocol(8 cycles of chemotherapy).Collected respectively before and after the last chemotherapy of peripheral blood,used flow cytometry technique to detect the proportion of T cell subsets and NK cells in peripheral blood,and compared the change of the part of the quality of life before and after chemotherapy.Results After chemotherapy of total of 66 patients CD3+ T cells,CD3+ CD4+T cells and NK cells of peripheral blood ((68.58± 11.03) ％,(33.53 ± 8.84) ％,(18.27 ± 10.65) ％) significantly lower than before chemotherapy ((74.03±13.04)％,(38.42±9.79)％,(19.83± 10.19)％),the differences were statistically significant(t =4.296,3.387,4.092,P＜ 0.05).Grouping was TAC protocol with AC-T,T cell subsets and NK cells before chemotherapy differences had no statistical significance.But after chemotherapy,CD3+ T cells,CD3+ CD4+T cells,CD3+CD8+ T cells and Karnofky score((64.63±10.01)％,(31.19±7.41)％,(24.66±7.40)％,(68.63± 5.100)％) of peripheral blood on TAC protocol were more decreased than AC-T protocol((72.29± 10.78)％,(35.74± 9.60) ％,(30.15 ± 11.12) ％,(77.29 ± 4.58) ％),the differences were statistically significant (t =2.99,2.15,2.35,2.237,P＜0.05).CD3+ CD4+/CD3+ CD8+ and NK cells were also decreased,but without statistical significance.The body quality of 66 patients was slightly increased after chemotherapy,but without statistical significance.Conclusion The body's immune function and the part of quality of the breast cancer patient's life have declined by chemotherapy drugs in varying degrees.Compared TAC,AC-T protocol has less influence on the immunological function and the part of living quality of patients with breast cancer.

Objective To investigate the correlation between methylation status and death-associated protein kinase 1 (DAPK1) in SiHa and Hela cell line of cervical carcinoma and intervention of DNA methyltransferase inhibitor 5-azacytidine on the expression of DAPK1 and the proliferation of the cells. Methods DAPK1 methylation status was analyzed using methylation-specific PCR methods. The expression of mRNA and protein of DAPK1 were analyzed by RT-PCR and SABC methods after the treatment with 5-azacytidine. MTT assay was used to observe the changes of proliferation activity of the cells after 5-azacytidine treatment. Results DAPK1 genes were methylated and did not express in SiHa cells in the cervical carcinoma. Its expression could be restored by 5-azacytidine. MTT assay showed 5-azacytidine could weaken the proliferation of cancerous cells. Conclusion DAPK1 methylation plays an important role in the carcinogenesis of cervical cells and can reexpress after the treatment with 5-azacytidine which also restored its inhibitory function on carcinoma.

BACKGROUND:Cerebral vascular malformations are the leading cause of hemorrhagic apoplexy in young adults, and the rupture and bleeding of malformed vessels may cause severe neurological dysfunction. The mechanism of cerebral vascular malformations remains unclear. Modern molecular biology studies have shown that, angiogenic growth factors are abnormal y expressed in cerebral vascular malformations.
OBJECTIVE:To evaluate differences in the expression of angiogenic growth factors in cerebral vascular malformations, and discuss the possible relationship between cerebral vascular malformations and angiogenic growth factors.
METHODS:Fifty patients with cerebral vascular malformations and fifty patients with intracerebral hemorrhage were included in this study. The expressions of angiogenic growth factor (vascular endothelial growth factor and transforming growth factor-α) in the cerebral vascular malformation specimens and the normal superficial temporal artery specimens were detected with immunohistochemical staining.
RESULTS AND CONCLUSION:In the normal superficial temporal artery of intracerebral hemorrhage patients, no expression of vascular endothelial growth factor and transforming growth factor-αwas found;in the vascular malformations, they were highly expressed (P<0.05). Compared with normal blood vessels, vascular endothelial growth factor and transforming growth factor-αexpression was significantly increased in patients with cerebral vascular malformations.

Background Meningothelial cells (MECs) occupy the predominant cell component of barrier between optic nerve and the cerebral spinal fluid,and any change of cerebral fluid components probably affects the MECs function and further impairs the optic nerve.Objective This study was designed to investigate the influence of glutamate,a potentially excitotoxic amino acid,to the functional changes of MECs and provide a theoretical evidence for clarifying the mechanism of optic nerve disorders.Methods Human MECs strains were cultured in vitro and prepared into cell suspension.The cells were inoculated to 96-well plates with the densities of 1 × 104/we11.The glutamate of 100,200,400,600,800 and 1 000 μmol/L was added into medium for 12,24,36,48 and 72 hours,respectively,and the cultured cells without glutamate were used as normal control group.MTS assay was employed to measure the proliferative rate (absorbency) of the cells.The regularly cultured MECs were divided into 600 μmol/L glutamate-treated group and normal control group and the cells were treated for 12 and 24 hours respectively,and the expression of superoxide dismutase (SOD) mRNA and heat shock protein 90 (HSP90) mRNA in the cells was detected by real-time PCR;the level of total anti-oxidative capacity (T-AOC) of the cells was processed by enzyme linked immunosorbent assay (ELISA),and the reactive oxygen species (ROS) production was determined by DCFH-DA probe.Results Cultured MECs grew well and formed 80％ confluence after 72 hours culture.The proliferative rate of the cells were gradually decreased with the increase of glutamate dose and the lapse of affected time,with significant differences among different concentrations of glutamate and various time points (F tration =52.501,P＜0.001;Ftime =8.505,P＜0.001).The relative expression level of SOD mRNA was significantly reduced in the glutamate-treated group compared with the normal control group in both 24 hours and 48 hours after culture (t =20.278,t =16.724,both at P＜0.001),and the expression of HSP90 mRNA in the cells was significantly lower in the glutamate-treated group than that in the normal control group in 24 hours after culture (t =5.065,P =0.002).No significant difference was found in T-AOC activity between glutamate-treated group and normal control group in 24 hours after culture ([30.835±2.094] nmol/(min · L) vs.[32.873±2.317] nmol/(min · L)) (t=1.599,P =1.414).In 48 hours after culture,T-AOC activity was (29.561 ± 1.831) nmol/(min · L) in the glutamate-treated group,which was significantly lower in comparison with normal control group (33.680±2.039) nmol/(min · L)(t =3.682,P =0.004).Fluorescence staining showed that the intensity of green fluorescence of ROS in MECs in the normal control group was weaker than that in the glutamate-treated group under the immunofluorescense microscope.The ROS level was 48.110± 1.712 and 40.982± 1.853 at 24 hours and 48 hours in the glutamate-treated cells,and which was significantly elevated in comparison with 36.608± 1.009 and 37.153 ± 1.424 in the normal control group (t=14.178,P＜0.001;t=4.012,P=0.002).Conclusions Glutamate inhibits the proliferation of MECs in vitro,and excitatory toxicity of glutamate on MECs probably is associated with oxidative stress response.

Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.