Low-dose radiation-induced demethylation of 3ß-HSD participated in the regulation of testosterone content.

The effects of low-dose radiation (LDR, ≤0.1 Gy) on living organisms have been the hot areas of radiation biology but do not reach a definitive conclusion yet. So far, few studies have adequately accounted for the male reproductive system responses to LDR, particularly the regulation of testosterone content. Hence, this study was designed to evaluate the effects of LDR on Leydig cells and testicular tissue, especially the ability to synthesize testosterone. We found that less than 0.2-Gy 60 Co gamma rays did not cause significant changes in the hemogram index and the body weight; also, pathological examination did not find obvious structural alterations in testis, epididymis, and other radiation-sensitive organs. Consistently, the results from in vitro showed that only more than 0.5-Gy gamma rays could induce remarkable DNA damage, cycle arrest, and apoptosis. Notably, LDR disturbed the contents of testosterone in mice serums and culture supernatants of TM3 cells and dose dependently increased the expression of 3ß-HSD. After cotreatment with trilostane (Tril), the inhibitor of 3ß-HSD, increased testosterone could be partially reversed. Besides, DNA damage repair-related enzymes, including DNMT1, DNMT3B, and Sirt1, were increased in irradiated TM3 cells, accompanying by evident demethylation in the gene body of 3ß-HSD. In conclusion, our results strongly suggest that LDR could induce obvious perturbation in the synthesis of testosterone without causing organic damage, during which DNA demethylation modification of 3ß-HSD might play a crucial role and would be a potential target to prevent LDR-induced male reproductive damage.

A nationally quasi-experimental study to assess the impact of partial organized breast and cervical cancer screening programme on participation and inequalities.

BACKGROUND: Organized breast and cervical cancer screening programme could only provide services at no cost for a fraction of socioeconomic-deprived women in China and other low-resource countries, however, little evidence exists for whether such a programme effectively affect the participation and inequalities at the population level. METHODS: We used individual-level data from a nationally cross-sectional survey in 2014-2015 for breast and cervical cancer screening participation. Data for intervention and comparison grouping were from 2009 to 2014 national breast and cervical cancer screening programme, and counties covered by the programme were divided into intervention group. We assessed the impact of the intervention on the participation rates and the magnitude of inequalities with two approaches: multivariable multilevel logistic regressions adjusting for individual- and region-level covariates; and a difference analysis combined with propensity score matching that estimated the average intervention effect. RESULTS: Of 69,875 included women aged 35-64 years, 21,620 were classified into the intervention group and 43,669 into the comparison group for breast cancer screening; and 31,794 into the intervention group, and 33,682 into the comparison group for cervical cancer screening. Participation rate was higher in intervention group than comparison group for breast cancer screening (25.3, 95% confidential interval [CI], 22.8-27.7%, vs 19.1, 17.4-20.7%), and cervical cancer screening (25.7, 23.8-27.7%, vs 21.5, 19.6-23.5%), respectively. Intervention significantly increased the likelihood of participation for both breast cancer and cervical cancer screening in overall women, rural women and urban women, whereas the effect was significantly higher in rural women than urban women. The average intervention effect on the participation rate was an increase of 7.5% (6.7-8.2%) for breast cancer screening, and 6.8% (6.1-7.5%) for cervical cancer screening, respectively. The inequalities were significantly decreased by 37-41% (P < 0.001) between rural and urban, however, were slightly decreased or even increased in terms of age, education status, and household income. CONCLUSIONS: Organized breast and cervical cancer screening programme targeting for a fraction of women could increase the participation rates at population level, however, it could not significantly affect socioeconomic-introduced inequalities. Further studies are need to conduct time-series analyses and strengthen the causal correlation.

Formation of ultracold 39K133Cs molecules via Feshbach optimized photoassociation.

A Feshbach optimized photoassociation (FOPA) process for preparing ultracold excited-state 39K133Cs molecules is studied theoretically. Under the joint action of the magnetic field and short laser pulse, the colliding atoms in a superposition state composed of eight hyperfine components are converted into a molecule in the vibrational level of the excited state via two transition processes, the transition between singlet states and the transition between triplet states. The association efficiency can be significantly enhanced by taking advantage of Feshbach resonance. At different resonance positions, different hyperfine components of the superposition state dominate over the FOPA process, and the quantum interference displays different behaviors. Compared with the FOPA process only including a single hyperfine component, the quantum interference in the FOPA process containing all hyperfine components has a visible effect on the association efficiency.

Bioinformatic analysis of a microRNA regulatory network in Huntington's disease.

Huntington's disease is an autosomal dominant hereditary neurodegenerative disease characterized by progressive dystonia, chorea and cognitive or psychiatric disturbances. The leading cause is the Huntington gene mutation on the patient's chromosome 4 that produces a mutated protein. Recently, attention has focused on the relationship between microRNAs and Huntington's disease's pathogenesis. In Huntington's disease, microRNAs can interact with various transcription factors; dysregulated microRNAs may be associated with the Cytosine deoxynucleotide-Adenine ribonucleotides-Guanine ribonucleotide length and Huntington's disease's progression and severity. This study explores the role of microRNAs in the pathogenesis of Huntington's disease through bioinformatics analysis. By analyzing data from the Gene Expression Omnibus database, we identified a total of 9 differentially expressed microRNA. Subsequently, target genes and long non-coding RNAs were predicted, and a comprehensive regulatory network centered on microRNA was constructed. The microRNA integrated regulatory network, Homo sapiens (hsa)-miR-144-3p, interacted with the largest number of long non-coding RNAs, including X-inactive specific transcript and taurine upregulated gene 1. The miRNAs, hsa-miR-10b-5p and hsa-miR-196a-5p, regulated most of the target genes, including class I homeobox and brain-derived neurotrophic factor genes. Additionally, 59 Gene Ontology terms and eight enrichment pathways were identified by analyzing the target genes of hsa-miR-196a-5p and hsa-microRNA-10b-5p. In conclusion, hsa-miR-10b-5p and hsa-miR-196a-5p were significantly and differentially expressed in Huntington's disease, the long non-coding RNAs X-inactive specific transcript, taurine upregulated gene 1, and target genes such as homeobox or brain-derived neurotrophic factor may play critical roles in the pathogenesis of Huntington's disease.

Histone acetyltransferase MOF is involved in suppression of endometrial cancer and maintenance of ERα stability.

Histone acetyltransferase MOF is involved in active transcription regulation through histone H4K16 acetylation. MOF is downexpressed in a number of human tumors, but biological function of MOF in endometrial cancer has not been fully defined. The estrogen receptor α (ERα) is a transcription factor that regulates estrogen-stimulated cell proliferation in hormone-responsive tumors. However, ERα expression is decreased in grade III ECa samples and high expression of ERα is associated with long disease-free survival in ECa. The molecular mechanism for these observations is still unclear. Here we demonstrate knockdown of MOF promotes ECa cell growth and proliferation in vitro and in vivo. Clinical evidence indicates that expression MOF is decreased and positively correlated with that of ERα in ECa tissues. Furthermore, MOF physically interacts with ERα and modulates ERα stability in ECa cells. In addition, MOF modulates expression of a subset of endogenous genes regulated by ERα. Taken together, our results define MOF as a potential tumor suppressor in ECa participates in maintenance of ERα protein stability and regulation of ERα action.

The modulating action of electric field on magnetically tuned Feshbach resonance.

We investigate the modulating action of an external electric field on the magnetically tuned Feshbach resonance in ultracold heteronuclear atomic collision by using the multichannel quantum-defect theory (MQDT). The coupling between different partial wave states induced by an electric field is included into the singlet and triplet quantum defect matrices y(0) and y(1). By taking the truncated -C6/R6 - C8/R8 - C10/R10 potential as the reference potential, the threshold behaviors of four quantum-defect parameters for the lowest three partial waves are described. The results calculated by using the MQDT agree with those calculated using the coupled channel method. Moreover, we present an analytical expression used for describing the variation of the position and width of the magnetically tuned Feshbach resonance modulated by an electric field.

Personal ultraviolet Radiation exposure in a cohort of Chinese mother and child pairs: the Chinese families and children study.

BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

Accurate calculations of weakly bound state energy and scattering length near magnetically tuned Feshbach resonance using the separable potential method.

We present a theoretical model for investigating the magnetically tuned Feshbach resonance (MTFR) of alkali metal atoms using the separable potential method (SPM). We discuss the relationship and difference between the SPM and the asymptotic bound state model. To demonstrate the validity of the SPM, we use it to calculate the weakly bound state energy and magnetically tuned scattering length for the 6Li-40K, 7Li2, and 6Li2 systems with narrow and broad Feshbach resonances. The results of the SPM calculations are in good agreement with those of coupled channel calculations and with experimental measurements for all three systems. The SPM, by simplifying the calculation of the two-body MTFR, is expected to simplify numerical computations for three-atom collisions in a magnetic field and the Feshbach-optimized photoassociation process.

High-rank separable atom-atom interaction potential used for solving two-body Lippmann-Schwinger and three-body Faddeev equations.

We derive a high-rank separable potential formula of the atom-atom interaction by using the two-body wave function in the coordinate space as inputs. This high-rank separable potential can be utilized to numerically solve the two-body Lippmann-Schwinger equation and three-body Faddeev equation. By analyzing the convenience and stability of numerical calculations for different kinds of the matrix forms of the Lippmann-Schwinger and Faddeev equations, we can find the optimal forms of the kernal matrices in the two- and three-body scattering equations. We calculate the dimer bound energy, two-body scattering phase shift and off-shell t-matrix, the trimer bound energy, atom-dimer scattering length, and three-body recombination rate using the high-rank separable potentials, taking the identical 4He atoms as an application example. All the calculations converge quickly for the rank number N ⩾ 3 . The high-rank separable potential is valid for two-body scattering calculation of 4He atoms, but not accurate enough for reproducing the three-body scattering results by using only two-body s-wave interaction and describing the contributions of two-body high partial-waves to the three-body scattering for the 4He3 system.

[The Relationship of Clinicopathology of p16 in Non-small Cell Lung Cancer and 5-nitrogen impurity-2'-deoxycytidine-nitrogen Impurity on the Influence of p16 Expression in Lung Cancer A549 Cells].

OBJECTIVE: To investigate the relationship between expression of tumor suppressor gene p16 in non-small cell lung cancer (NSCLC) tissues and clinicopathological parameters,to further study on DNA methyltransferase inhibitors 5-nitrogen impurity-2'-deoxycytidine (5-Aza-CdR) in human lung cancer cell line A549 in regulating the expression of p16. METHODS: The expression of p16 protein in 76 cases of NSCLC tissues and normal tissue adjacent to carcinoma were detect by immunohistochemical SP method and the differences of p16 protein expression were analyzed. p16 gene promoter region of DNA methylation status were detect by MSP method in 5-Aza-CdR processing A549 cells,the expression of p16 in A549 lung cancer cell and effect of 5-Aza-CdR were detect by Western blot method. RESULTS: 32 cases (42.11%) of p16 protein expression was positive,significantly lower than that of the normal tissue adjacent to carcinoma (positive expression in 59 cases,77.63%) in 76 cases of NSCLC tissues; There were statistically significant differences (P<0.05) in the positive expression rates of p16 in NSCLC tissues with different pathological tissue grading,tumor differentiation degree,clinical TNM stage and lymph node metastasis. In A549 cells,p16 protein expression and non-methylated products were both in low expression states. After treated with 5-Aza-CdR,the expression of p16 protein and its non-methylated products were up-regulated,with the increase of 5-Aza-CdR concentration. CONCLUSION: The low expression of p16 in NSCLC tissues with squamous cell carcinomas,low differentiation,lymph node metastasis and phase Ⅲ-Ⅳ,which may prompt the deactivation and cause further progression of NSCLC,5-Aza-CdR could induce the expression of p16 protein and non-methylated products in A549 cells.

Cold atom-atom-ion three-body recombination of 4He-4He-X- (X = H or D).

The atom-atom-ion three-body recombination (TBR) of mixed 4He and X- (X = H or D) systems is investigated by solving the Schrödinger equation using the adiabatic hyperspherical representation method. It is shown that the dominant products after a TBR in the ultracold limit (E ≤ 0.1 mK × kB) are different for the two systems. For the 4He4HeH- system, the rate of TBR into the 4HeH- ion is nearly two orders of magnitude larger than that of TBR into the neutral 4He2 molecule. In contrast, the yield of 4He2 is a little higher than that of 4HeD- for the 4He4HeD- system. Furthermore, since the adiabatic potentials become more attractive and the nonadiabatic couplings become much stronger by substituting D for H in the 4He4HeH- system, the total TBR rate for the 4He4HeD- system is nearly two orders of magnitude larger than that for the 4He4HeH- system.

Role of sharp avoided crossings in short hyper-radial range in recombination of the cold 4He3 system.

The role of sharp avoided crossings (SACs) in a short hyper-radial range R≤ 50 a.u. in the calculation of recombination for a cold 4He3 system is investigated in the adiabatic hyperspherical representation by "turning off and on" the relevant nonadiabatic couplings. The influence of SACs on the recombination is related with the channels of the system and with the scattering energy. For JΠ = 0+ symmetry, the two-body recombination channel has an attractive potential well, which makes radial wave functions of both two-body recombination channel and three-body continuum channels accessible in the short hyper-radial range where SACs are located. The SACs consequently play an important role in coupled-channel calculations and this is particularly the case for lower scattering energies. However, for excited nuclear orbital momenta, i.e., JΠ = 1-, 2+,…, 7- symmetries, the two-body recombination channel has a repulsive interaction and the radial wave functions are not accessible in the short hyper-radial range. Therefore, omission of SACs in the short range for these symmetries has no effect on the numerical results, which leads to great savings on hyper-radial grid points in the practical numerical calculations. Moreover, to make the nonadiabatic couplings among channels to be continuous in the hyper-radius, different methods associated with the application of consistent phase convention are discussed.

Molecular alignment effect on the photoassociation process via a pump-dump scheme.

The photoassociation processes via the pump-dump scheme for the heternuclear (Na + H → NaH) and the homonuclear (Na + Na → Na2) molecular systems are studied, respectively, using the time-dependent quantum wavepacket method. For both systems, the initial atom pair in the continuum of the ground electronic state (X(1)Σ(+)) is associated into the molecule in the bound states of the excited state (A(1)Σ(+)) by the pump pulse. Then driven by a time-delayed dumping pulse, the prepared excited-state molecule can be transferred to the bound states of the ground electronic state. It is found that the pump process can induce a superposition of the rovibrational levels |v, j〉 on the excited state, which can lead to the field-free alignment of the excited-state molecule. The molecular alignment can affect the dumping process by varying the effective coupling intensity between the two electronic states or by varying the population transfer pathways. As a result, the final population transferred to the bound states of the ground electronic state varies periodically with the delay time of the dumping pulse.

Accuracy of real-time tissue elastography for the evaluation of hepatic fibrosis in patients with chronic hepatitis B: a prospective multicenter study.

BACKGROUND: The prognosis and management of hepatic fibrosis are closely related to the stage of the disease. The limitations of liver biopsy, which is the gold standard for treatment, include its invasiveness and sampling error. Ultrasound elasticity might be the most promising imaging technology for the noninvasive and accurate assessment of hepatic fibrosis. Real-time tissue elastography (RTE) measures the relative stiffness of the tissue in the region of interest caused by the heartbeat. Many studies have verified that RTE is useful for the diagnosis of hepatic fibrosis in patients with chronic hepatitis C (CHC). PURPOSE: To determine the formula of the liver fibrosis index for chronic hepatitis B (BLFI) and to validate the diagnostic accuracy of the BLFI for hepatic fibrosis compared with the liver fibrosis index (LFI). MATERIALS AND METHODS: RTE was performed in 747 prospectively enrolled patients with chronic hepatitis B (CHB) or cirrhosis from 8 centers in China; 375 patients were analyzed as the training set, and 372 patients were evaluated as the validation set. The fibrosis stage was diagnosed from pathological specimens obtained by ultrasound-guided liver biopsy. Nine image features were measured from strain images, and the new formula for the BLFI was obtained by combining the nine imaging features of the RTE images using multiple regression analysis of the training set. The BLFI and LFI were compared with the pathological fibrosis stage at diagnosis, and the diagnostic performances of the indexes were compared. RESULTS: The Spearman correlation coefficient between the BLFI and hepatic fibrosis stages was significantly positive (r = 0.711, p < 0.001), and significant differences were present between all disease stages. The areas under the receiver-operating characteristic (AUROC) curves of the BLFI and LFI for predicting significant fibrosis (S0-S1 vs. S2-S4) were 0.858 and 0.858, respectively. For cirrhosis (S0-S3 vs. S4), the AUROC curves of the BLFI and LFI were 0.868 and 0.862, respectively. CONCLUSION: The results of this large, multicenter study confirmed that RTE is valuable for the diagnosis of hepatic fibrosis in patients with CHB. However, the diagnostic efficiencies of the new BLFI and the original LFI, which were based on CHC, for the assessment of CHB hepatic fibrosis were similar; thus, the LFI has the potential to be used to directly evaluate the extent of hepatic fibrosis in patients with CHB.

The influence of field-free orientation on the predissociation dynamics of the NaI molecule.

The orientation and predissociation dynamics of the NaI molecule are studied by using a time-dependent wavepacket method. The NaI molecule is first pre-oriented by a single-cycle pulse (SCP) in terahertz (THz) region and then predissociated by a femtosecond pump pulse. The influence of the molecular field-free orientation on the predissociation dynamics is studied in detail. We calculate the radial and angular distributions, the molecular orientation degrees, and the time-dependent populations for both the ground and excited electronic states. It is found that the pre-orientation affects the angular distributions significantly, and that it has weak influence on the radial distributions. By varying the delay time between the THz SCP and the pump pulse, the angular distribution of the fragments from the predissociation can be manipulated.

Optimal control of charge transfer for slow H+ + D collisions with shaped laser pulses.

We show that optimally shaped laser pulses can beneficially influence charge transfer in slow H(+)+D collisions. Time-dependent wave packet optimal control simulations are performed based on a two-state adiabatic Hamiltonian. Optimal control is performed using either an adaptive or a fixed target to obtain the desired laser control field. In the adaptive target scheme, the target state is updated according to the renormalized fragmentary yield in the exit channel throughout the optimization process. In the fixed target scheme, the target state in the exit channel is a normalized outgoing Gaussian wave packet located at a large internuclear separation. Both approaches produced excellent optimal outcomes, far exceeding that achieved in the field-free collisional charge transfer. The adaptive target scheme proves to be more efficient, and often with complex final wave packet. In contrast, the fixed target scheme, although more slowly convergent, is found to produce high fidelity for the desired target wave packet. The control mechanism in both cases utilizes bound vibrational states of the transient HD(+) complex.

Corrigendum to "Potential pre-COPD indicators in association with COPD development and COPD prediction models in Chinese: a prospective cohort study" [The Lancet Regional Health - Western Pacific 44 (2024) 100984].

[This corrects the article DOI: 10.1016/j.lanwpc.2023.100984.].

Potential pre-COPD indicators in association with COPD development and COPD prediction models in Chinese: a prospective cohort study.

Background: Lung injury might take place before chronic obstructive pulmonary disease (COPD) occurs. A clearer definition of "pre-COPD" based on the effects of potential indicators on increasing risk of COPD development and a prediction model involving them are lacking. Methods: A total of 3526 Chinese residents without COPD aged 40 years or older derived from the national cross-sectional survey of COPD surveillance in 2014-2015 were followed up for a mean of 3.59 years. We examined the associations of chronic bronchitis, preserved ratio impaired spirometry (PRISm), low peak expiratory flow (PEF), spirometric small airway dysfunction (sSAD), low maximal mid-expiratory flow (MMEF), low forced expiratory flow 50% of pulmonary volume (FEF50), and low FEF75 with subsequent COPD and constructed a prediction model with LASSO-Cox regression. Findings: 235 subjects in the cohort developed COPD during the follow-up. Subjects with PRISm, low PEF, sSAD, low MMEF, low FEF50, and low FEF75 had an increased risk of developing COPD (adjusted hazard ratio [HR] ranging from 1.57 to 3.01). Only chronic bronchitis (HR 2.84 [95% CI 1.38-5.84] and 2.94 [1.43-6.04]) and sSAD/low MMEF (HR 2.74 [2.07-3.61] and 2.38 [1.65-3.43]) showed effects independent of the other indicators and their concurrence had the strongest effect (HR 5.89 and 4.80). The prediction model including age, sex, low MMEF, low FEF50, and indoor exposure to biomass had good performance both internally and temporally. The corrected C-index was 0.77 (0.72-0.81) for discrimination in internal validation. For temporal validation, the area under the receiver operating characteristic curve was 0.73 (0.63-0.83). Good calibration was indicated in plot for internal validation and by Hosmer-Lemeshow test for temporal validation. Interpretation: Individuals with concurrent chronic bronchitis and sSAD/low MMEF indicating pre-COPD optimally require more high attention from physicians. Our prediction model could serve as a multi-dimension tool to predict COPD comprehensively. Funding: The Ministry of Finance and the Ministry of Science and Technology of the People's Republic of China and the National Natural Science Foundation of China.

Assessing interventions to encourage primary care health workers to recommend influenza vaccination and the impact on vaccination uptake for persons with Non-Communicable diseases in China.

BACKGROUND: Influenza vaccination coverage is low among persons with non-communicable diseases (NCDs) in China. Chinese health workers (HWs) do not routinely recommend influenza vaccination despite evidence that recommendations increase vaccine uptake. This study aims to assess whether interventions increased primary care HWs' recommendation for influenza vaccination and measure their impact on influenza vaccine uptake in persons with NCDs. METHODS: We conducted a cluster randomized controlled study in public primary healthcare clinics in Hubei from November 2018 through April 2019. In the intervention clinics, primary care HWs received training on the benefits of influenza vaccination and were asked to recommend influenza vaccine in routine primary healthcare for persons with NCDs. In the control clinics, primary care HWs did not receive training and provided standard services. We conducted questionnaire surveys before and after the intervention to collect information about recommendations made and receipt of influenza vaccines. RESULTS: A total of 896 primary care HWs and 4552 persons with NCDs were included. After intervention, a higher percentage of HWs recommended influenza vaccines in intervention clinics compared to control clinics. Vaccinated primary care HWs were more likely to recommend vaccination. Persons with NCDs reported higher influenza vaccination coverage in intervention than control clinics, and primary care HWs' recommendation increased vaccination uptake among persons with NCDs. CONCLUSIONS: Vaccinated primary care HWs were more likely to recommend influenza vaccination than unvaccinated HWs. Promoting primary care HWs' vaccination and encouraging them to recommend influenza vaccination during routine primary healthcare could increase influenza vaccine receipt among persons with NCDs. Registration number ChiCTR2200067140.

Chemokine fractalkine attenuates overactivation and apoptosis of BV-2 microglial cells induced by extracellular ATP.

Microglia, the resident macrophages of the central nervous system (CNS), are activated by a myriad of signaling molecules including ATP, an excitatory neurotransmitter and neuron-glial signal with both neuroprotective and neurotoxic effects. The "microglial dysfunction hypothesis" of neurodegeneration posits that overactivated microglia have a reduced neuroprotective capacity and instead promote neurotoxicity. The chemokine fractalkine (FKN), one of only two chemokines constitutively expressed in the CNS, is neuroprotective in several in vivo and in vitro models of CNS pathology. It is possible, but not yet demonstrated, that high ATP concentrations induce microglial overactivation and apoptosis while FKN reduces ATP-mediated microglial overactivation and cytotoxicity. In the current study, we examined the effects of FKN on ATP-induced microglial apoptosis and the underlying mechanisms in the BV-2 microglial cell line. Exposure to ATP induced a dose-dependent reduction in BV-2 cell viability. Prolonged exposure to a high ATP concentration (3 mM for 2 h) transformed ramified (quiescent) BV-2 cells to the amoebic state, induced apoptosis, and reduced Akt phosphorylation. Pretreatment with FKN significantly inhibited ATP-induced microglial apoptosis and transformed amoebic microglia to ramified quiescent cells. These protective effects were blocked by chemical inhibition of PI3 K, strongly implicating the PI3 K/Akt signaling pathway in FKN-mediated protection of BV-2 cells from cytotoxic ATP concentrations. Prevention of ATP-induced microglial overactivation and apoptosis may enhance the neuroprotective capacity of these cells against both acute insults and chronic CNS diseases.