AIM: To examine the protection of ferulic acid(FA) against ionizing radiation(IR)-induced lens injury in rats, as well as the underlying mechanisms.METHODS: FA(50 mg/kg) was administered to rats for 4 consecutive days...AIM: To examine the protection of ferulic acid(FA) against ionizing radiation(IR)-induced lens injury in rats, as well as the underlying mechanisms.METHODS: FA(50 mg/kg) was administered to rats for 4 consecutive days before they were given 10 Gy γ-radiation, as well as for 3 consecutive days afterward. Two weeks after radiation, the eye tissues were collected. Histological alterations were evaluated by hematoxylineosin staining. Enzyme linked immunosorbent assay(ELISA) was utilized to assess the activities of glutathione reductase(GR) and superoxide dismutase(SOD), as well as the levels of glutathione(GSH) and malondialdehyde(MDA) in the lenses. The protein and m RNA levels of Bcl-2, caspase-3, Bax, heme oxygenase-1(HO-1), and glutamatecysteine ligase catalytic subunit(GCLC) were quantified using Western blot and quantitative reverse transcription polymerase chain reaction, respectively. With nuclear extracts, the nuclear factor erythroid-2 related factor(Nrf2) protein expressions in the nuclei were also measured.RESULTS: Rats exposed to IR showed lens histological alterations which could be alleviated by FA. FA treatment reversed apoptosis-related markers in IR-induced lens, as evidenced by lower levels of Bax and caspase-3 and higher level of Bcl-2. Furthermore, IR induced oxidative damage manifested by decreased GSH level, increased MDA level, and decreased SOD and GR activities. FA boosted nuclear translocation of Nrf2 and increased the expressions of HO-1 and GCLC to inhibit oxidative stress, as evidenced by an increase in GSH, a decrease in MDA, and an increase in GR and SOD activities.CONCLUSION: FA may work well in preventing and treating IR-induced cataract through promoting the Nrf2 signal pathway to attenuate oxidative damage and cell apoptosis.展开更多
The field-ionization Coulomb explosion model is extended to investigate the multielectron dissociative ionization process of N2 molecule irradiated by an intense femtosecond laser field with an arbitrary polarization....The field-ionization Coulomb explosion model is extended to investigate the multielectron dissociative ionization process of N2 molecule irradiated by an intense femtosecond laser field with an arbitrary polarization. The ionization process of N2 molecule is found to be optimal at the critical internuclear distance Rc=7a.u., which is independent of the laser polarization state, the molecular explosion channel and the angle between the molecular axis and the direction of laser electric field. The kinetic energies of the ion fragments are identical in the cases of linear and circular polarizations at the same incident laser intensity. However, the probability of electron ionization is very sensitive to the above three parameters. At the critical distance Rc=7a.u. the angular dependence of the threshold intensity for the over-the-barrier ionization leads to the geometric alignment of molecules in the case of linear polarization. The threshold intensity in the case of circular polarization is apparently higher than that in the case of linear polarization, which can well explain the significant decrease of ionization in the case of circular polarization. The numerical calculations are compared with the experimental measurements.展开更多
Because of the discrete charge storage mechanism, charge trapping memory(CTM) technique is a good candidate for aerospace and military missions. The total ionization dose(TID) effects on CTM cells with Al2O3/HfO2/...Because of the discrete charge storage mechanism, charge trapping memory(CTM) technique is a good candidate for aerospace and military missions. The total ionization dose(TID) effects on CTM cells with Al2O3/HfO2/Al2O3(AHA) high-k gate stack structure under in-situ 10 keV x-rays are studied. The C-V characteristics at different radiation doses demonstrate that charge stored in the device continues to be leaked away during the irradiation,thereby inducing the shift of flat band voltage(V(fb)). The dc memory window shows insignificant changes, suggesting the existence of good P/E ability. Furthermore, the physical mechanisms of TID induced radiation damages in AHA-based CTM are analyzed.展开更多
By means of the energy level formula E(p)=α+2βcos(pπ/(n+t+1)). the pseudo π ionization potentials of H-(CH_2)_n-X (X=H, F, Cl, Br, I, OH, and SH) are identified by optimizing linear regression analysis, from which...By means of the energy level formula E(p)=α+2βcos(pπ/(n+t+1)). the pseudo π ionization potentials of H-(CH_2)_n-X (X=H, F, Cl, Br, I, OH, and SH) are identified by optimizing linear regression analysis, from which α=13.54±0.50eV and β=1.75±0.13eV are obtained.展开更多
We perform a kinetically complete measurement on the fragmentation of Coulomb explosion of 1-120 molecules in intense few-cycle linearly and circularly polarized laser fields. Both the fragmentations of 1t203+ and H...We perform a kinetically complete measurement on the fragmentation of Coulomb explosion of 1-120 molecules in intense few-cycle linearly and circularly polarized laser fields. Both the fragmentations of 1t203+ and H204+ reveal the concerted pathway of dissociation. The length of the OH bond prior to the Coulomb explosion of both molecular ions is sensitive to the laser pulse duration and laser intensity. However, the bending angle of H-O-H is less sensitive to the pulse duration and laser intensity. We introduce the mechanism of charge resonance enhanced double ionization to elucidate the triple (or quadruple) dissociative ionization dynamics of H20, in which two electrons are non-adiabatically localized at the protons of the precursor ion H2O^+ (or H2O^2+) and are released simultaneously due to the over barrier ionization in the combined laser field and molecular ionic potential. Such charge resonance enhanced multiple ionization is not suppressed in few-cycle laser fields and elliptically polarized laser fields.展开更多
Covalent organic frameworks(COFs),with two dimensional(2D-)or three dimensional(3D-)structures,have accessible open channels or nanopores,with uniform sizes ranging from angstroms to nanometers and have emerged as an ...Covalent organic frameworks(COFs),with two dimensional(2D-)or three dimensional(3D-)structures,have accessible open channels or nanopores,with uniform sizes ranging from angstroms to nanometers and have emerged as an excellent and promising platform for designing catalysts or catalyst carriers.Herein,a 2 D-COF grafted with a 1-alkyl-3-methylimidazolium-based ionic liquid(AMIMBr@H2 P-DHPh COF)on the channel walls was synthesized and utilized as a highly efficient heterogeneous catalyst for the chemical fixation of CO2 via a reaction with epoxides under solvent-free and co-catalyst-free conditions.The as-synthesized AMIMBr@H2 P-DHPh COF shows excellent catalytic activity in promoting the cycloaddition reactions between epoxide and CO2;the excellent catalytic activity was maintained for up to five cycles.Advantages like high porosity,functional versatility,easy modification of COFs,and high catalytic activity of ionic liquids,have been realized in a single material.展开更多
Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.Methods Protein expression levels were assessed by western blot in the hu...Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation.Depletion of p21 was carried out by employing the siR NA technique.Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28,an M-phase marker.Senescence was assessed by senescenceassociated-β-galactosidase(SA-β-gal) staining combined with Ki67 staining,a cell proliferation marker.Results Accompanying increased p21,the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays.Furthermore,these irradiated cells were blocked at the G2 phase followed by cellular senescence.Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases,as well as the high expression of histone H3 phosphorylated at Ser28.Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells.However,cells with serious DNA damage failed to undergo cytokinesis,leading to the accumulation of multinucleated cells.Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation.Downregulation of p21 by siR NA resulted in G2-arrested cells entering into mitosis with serious DNA damage.This is the first report on elucidating the role of p21 in the bypass of mitosis.展开更多
The ionization energies (IEs) of cyclopropenylidene (c-C3H2), propargylene (HCCCH) and propadienylidene (H2CCC) have been computed using the CCSD(T)/CBS method, which involves the approxixnation to the compl...The ionization energies (IEs) of cyclopropenylidene (c-C3H2), propargylene (HCCCH) and propadienylidene (H2CCC) have been computed using the CCSD(T)/CBS method, which involves the approxixnation to the complete basis set (CBS) limit at the coupled cluster level with single and double excitations plus quasi-perturbative triple excitation effect (CCSD(T)). The zero-point vibrational energy correction, the core-valence electronic correction, the scalar relativistic effect and the high level correction beyond the CCSD(T) excitations have also been made in these calculations. The CCSD(T)/CBS values for the IN(c-C3H2) and IE(HCCCH) of 9.164, 8.987 eV are in good agreement with the experimental values of (9.15±0.03) and (8.96±0.04) eV. The CCSD(T)/CBS calculations yield the IE values of 10.477 and 10.388 eV for the ionization transitions H2CCC→H2CCC^+ (^2A1, C2v) and H2CCC→H2CCC+ (^2A', Cs), respectively. On the basis of the Franek-Condon factor consideration, the IE of (10.43±0.02) eV determined in the previous single-photon ionization experiment most likely corresponds to the ionization threshold for the H2CCC→H2CCC^+(^2A1, C2v) transition. Although the precision of the experimental IN measurements fpr c-C3H2, HCCCH, and H2CCC is insufficient to pin down the accuracy of the theoretical calculations to better than ±30 meV, the excellent agreement between the experimental and theoretical IE values observed in the present study indicates that the CCSD(T)/CBS calculations together with high-order correlation corrections are capable of yielding reliable IE predictions for simple hydrocarbon carbenes and bi-radicals. We have also reported the heats of formation at 0 K (△H^of0) and 298 K (△H^of298)for c-C3H2/c-C3H2^+, HCCCH/HCCCH^+, and H2CCC/H2CCC^+, The available experimental △H^of0 and △H^of298 values for c-C3H2/c C3H2^+, HCCCH/HCCCH^+ are found to be in good accord with the CCSD(T)/CBS predictions after taking into account the experimental uncertainties.展开更多
The branching ratios of ions and the angular distributions of electrons ejected from the Eu 4f^76p_(1/2)nd auto-ionizing states are investigated with the velocity-map-imaging technique.To populate the above auto-ion...The branching ratios of ions and the angular distributions of electrons ejected from the Eu 4f^76p_(1/2)nd auto-ionizing states are investigated with the velocity-map-imaging technique.To populate the above auto-ionizing states,the relevant bound Rydberg states have to be detected first.Two new bound Rydberg states are identified in the region between41150 cm^(-1)and 44580 cm^(-1),from which auto-ionization spectra of the Eu 4f^76p_(1/2)nd states are observed with isolated core excitation method.With all preparations above,the branching ratios from the above auto-ionizing states to different final ionic states and the angular distributions of electrons ejected from these processes are measured systematically.Energy dependence of branching ratios and anisotropy parameters within the auto-ionization spectra are carefully analyzed,followed by a qualitative interpretation.展开更多
The paper is devoted to the proof of the uniqueness theorem for solution of the equation for the non-local ionization source in a glow discharge and a hollow cathode in general 3D geometry. The theorem is applied to w...The paper is devoted to the proof of the uniqueness theorem for solution of the equation for the non-local ionization source in a glow discharge and a hollow cathode in general 3D geometry. The theorem is applied to wide class of electric field configurations, and to the walls of discharge volume, which have a property of incomplete absorption of the electrons. Cathode is regarded as interior singular source, which is placed arbitrarily close to the wall. The existence of solution is considered also. During the proof of the theorem many of useful structure formulae are obtained. Elements of the proof structure, which have arisen, are found to have physical sense. It makes clear physical construction of non-local electron avalanche, which builds a source of ionization in glow discharge at low pressures. Last has decisive significance to understand the hollow cathode discharge configuration and the hollow cathode effect.展开更多
Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora...Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237(MLN)and/or p21 depletion by small interfering RNA(si RNA).Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator(FUCCI)system combined with histone H3 phosphorylation at Ser10(p S10 H3)detection.Senescence was assessed using senescence-associated-β-galactosidase(SA-β-Gal),Ki67,andγH2AX staining.Protein expression levels were determined using western blotting.Results Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment.The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells,ultimately leading to senescence in G1.During this process,the p53/p21 pathway is hyperactivated.Accompanying p21 accumulation,Aurora A kinase levels declined sharply.MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.Conclusion Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation,leading to senescence via mitotic skipping.展开更多
基金Supported by Medical Science Foundation of Military for Young Scholars (No.19QNP064)Natural Science Foundation of Jiangsu Province (No.BK20191233)Jiangsu Funding Program for Excellent Postdoctoral Talent (No.2022ZB702)。
文摘AIM: To examine the protection of ferulic acid(FA) against ionizing radiation(IR)-induced lens injury in rats, as well as the underlying mechanisms.METHODS: FA(50 mg/kg) was administered to rats for 4 consecutive days before they were given 10 Gy γ-radiation, as well as for 3 consecutive days afterward. Two weeks after radiation, the eye tissues were collected. Histological alterations were evaluated by hematoxylineosin staining. Enzyme linked immunosorbent assay(ELISA) was utilized to assess the activities of glutathione reductase(GR) and superoxide dismutase(SOD), as well as the levels of glutathione(GSH) and malondialdehyde(MDA) in the lenses. The protein and m RNA levels of Bcl-2, caspase-3, Bax, heme oxygenase-1(HO-1), and glutamatecysteine ligase catalytic subunit(GCLC) were quantified using Western blot and quantitative reverse transcription polymerase chain reaction, respectively. With nuclear extracts, the nuclear factor erythroid-2 related factor(Nrf2) protein expressions in the nuclei were also measured.RESULTS: Rats exposed to IR showed lens histological alterations which could be alleviated by FA. FA treatment reversed apoptosis-related markers in IR-induced lens, as evidenced by lower levels of Bax and caspase-3 and higher level of Bcl-2. Furthermore, IR induced oxidative damage manifested by decreased GSH level, increased MDA level, and decreased SOD and GR activities. FA boosted nuclear translocation of Nrf2 and increased the expressions of HO-1 and GCLC to inhibit oxidative stress, as evidenced by an increase in GSH, a decrease in MDA, and an increase in GR and SOD activities.CONCLUSION: FA may work well in preventing and treating IR-induced cataract through promoting the Nrf2 signal pathway to attenuate oxidative damage and cell apoptosis.
基金Project supported by the National Key Basic Research Special Foundation (NKBRSF) (Grant No TG1999075207) and the National Natural Science Foundation of China (Grant Nos 10104003, 90206003 and 60378012) and the China Postdoctoral Science Foundation (Grant No 2003034093).
文摘The field-ionization Coulomb explosion model is extended to investigate the multielectron dissociative ionization process of N2 molecule irradiated by an intense femtosecond laser field with an arbitrary polarization. The ionization process of N2 molecule is found to be optimal at the critical internuclear distance Rc=7a.u., which is independent of the laser polarization state, the molecular explosion channel and the angle between the molecular axis and the direction of laser electric field. The kinetic energies of the ion fragments are identical in the cases of linear and circular polarizations at the same incident laser intensity. However, the probability of electron ionization is very sensitive to the above three parameters. At the critical distance Rc=7a.u. the angular dependence of the threshold intensity for the over-the-barrier ionization leads to the geometric alignment of molecules in the case of linear polarization. The threshold intensity in the case of circular polarization is apparently higher than that in the case of linear polarization, which can well explain the significant decrease of ionization in the case of circular polarization. The numerical calculations are compared with the experimental measurements.
基金Supported by the National Natural Science Foundation of China under Grant No 616340084the Youth Innovation Promotion Association of Chinese Academy of Sciences under Grant No 2014101+1 种基金the International Cooperation Project of Chinese Academy of Sciencesthe Austrian-Chinese Cooperative R&D Projects under Grant No 172511KYSB20150006
文摘Because of the discrete charge storage mechanism, charge trapping memory(CTM) technique is a good candidate for aerospace and military missions. The total ionization dose(TID) effects on CTM cells with Al2O3/HfO2/Al2O3(AHA) high-k gate stack structure under in-situ 10 keV x-rays are studied. The C-V characteristics at different radiation doses demonstrate that charge stored in the device continues to be leaked away during the irradiation,thereby inducing the shift of flat band voltage(V(fb)). The dc memory window shows insignificant changes, suggesting the existence of good P/E ability. Furthermore, the physical mechanisms of TID induced radiation damages in AHA-based CTM are analyzed.
文摘By means of the energy level formula E(p)=α+2βcos(pπ/(n+t+1)). the pseudo π ionization potentials of H-(CH_2)_n-X (X=H, F, Cl, Br, I, OH, and SH) are identified by optimizing linear regression analysis, from which α=13.54±0.50eV and β=1.75±0.13eV are obtained.
基金Supported by the National Basic Research Program of China under Grant No 2013CB922403the National Natural Science Foundation of China under Grant Nos 11125416,11434002,11121091 and 11134001
文摘We perform a kinetically complete measurement on the fragmentation of Coulomb explosion of 1-120 molecules in intense few-cycle linearly and circularly polarized laser fields. Both the fragmentations of 1t203+ and H204+ reveal the concerted pathway of dissociation. The length of the OH bond prior to the Coulomb explosion of both molecular ions is sensitive to the laser pulse duration and laser intensity. However, the bending angle of H-O-H is less sensitive to the pulse duration and laser intensity. We introduce the mechanism of charge resonance enhanced double ionization to elucidate the triple (or quadruple) dissociative ionization dynamics of H20, in which two electrons are non-adiabatically localized at the protons of the precursor ion H2O^+ (or H2O^2+) and are released simultaneously due to the over barrier ionization in the combined laser field and molecular ionic potential. Such charge resonance enhanced multiple ionization is not suppressed in few-cycle laser fields and elliptically polarized laser fields.
文摘Covalent organic frameworks(COFs),with two dimensional(2D-)or three dimensional(3D-)structures,have accessible open channels or nanopores,with uniform sizes ranging from angstroms to nanometers and have emerged as an excellent and promising platform for designing catalysts or catalyst carriers.Herein,a 2 D-COF grafted with a 1-alkyl-3-methylimidazolium-based ionic liquid(AMIMBr@H2 P-DHPh COF)on the channel walls was synthesized and utilized as a highly efficient heterogeneous catalyst for the chemical fixation of CO2 via a reaction with epoxides under solvent-free and co-catalyst-free conditions.The as-synthesized AMIMBr@H2 P-DHPh COF shows excellent catalytic activity in promoting the cycloaddition reactions between epoxide and CO2;the excellent catalytic activity was maintained for up to five cycles.Advantages like high porosity,functional versatility,easy modification of COFs,and high catalytic activity of ionic liquids,have been realized in a single material.
基金supported by the National Natural Science Foundation of China[No.U1232125,31270895]the International Science&Technology Cooperation Program of China[No.2015DFR30940]
文摘Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation.Depletion of p21 was carried out by employing the siR NA technique.Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28,an M-phase marker.Senescence was assessed by senescenceassociated-β-galactosidase(SA-β-gal) staining combined with Ki67 staining,a cell proliferation marker.Results Accompanying increased p21,the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays.Furthermore,these irradiated cells were blocked at the G2 phase followed by cellular senescence.Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases,as well as the high expression of histone H3 phosphorylated at Ser28.Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells.However,cells with serious DNA damage failed to undergo cytokinesis,leading to the accumulation of multinucleated cells.Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation.Downregulation of p21 by siR NA resulted in G2-arrested cells entering into mitosis with serious DNA damage.This is the first report on elucidating the role of p21 in the bypass of mitosis.
文摘The ionization energies (IEs) of cyclopropenylidene (c-C3H2), propargylene (HCCCH) and propadienylidene (H2CCC) have been computed using the CCSD(T)/CBS method, which involves the approxixnation to the complete basis set (CBS) limit at the coupled cluster level with single and double excitations plus quasi-perturbative triple excitation effect (CCSD(T)). The zero-point vibrational energy correction, the core-valence electronic correction, the scalar relativistic effect and the high level correction beyond the CCSD(T) excitations have also been made in these calculations. The CCSD(T)/CBS values for the IN(c-C3H2) and IE(HCCCH) of 9.164, 8.987 eV are in good agreement with the experimental values of (9.15±0.03) and (8.96±0.04) eV. The CCSD(T)/CBS calculations yield the IE values of 10.477 and 10.388 eV for the ionization transitions H2CCC→H2CCC^+ (^2A1, C2v) and H2CCC→H2CCC+ (^2A', Cs), respectively. On the basis of the Franek-Condon factor consideration, the IE of (10.43±0.02) eV determined in the previous single-photon ionization experiment most likely corresponds to the ionization threshold for the H2CCC→H2CCC^+(^2A1, C2v) transition. Although the precision of the experimental IN measurements fpr c-C3H2, HCCCH, and H2CCC is insufficient to pin down the accuracy of the theoretical calculations to better than ±30 meV, the excellent agreement between the experimental and theoretical IE values observed in the present study indicates that the CCSD(T)/CBS calculations together with high-order correlation corrections are capable of yielding reliable IE predictions for simple hydrocarbon carbenes and bi-radicals. We have also reported the heats of formation at 0 K (△H^of0) and 298 K (△H^of298)for c-C3H2/c-C3H2^+, HCCCH/HCCCH^+, and H2CCC/H2CCC^+, The available experimental △H^of0 and △H^of298 values for c-C3H2/c C3H2^+, HCCCH/HCCCH^+ are found to be in good accord with the CCSD(T)/CBS predictions after taking into account the experimental uncertainties.
基金Project supported by the National Natural Science Foundation of China(Grant No.11174218)
文摘The branching ratios of ions and the angular distributions of electrons ejected from the Eu 4f^76p_(1/2)nd auto-ionizing states are investigated with the velocity-map-imaging technique.To populate the above auto-ionizing states,the relevant bound Rydberg states have to be detected first.Two new bound Rydberg states are identified in the region between41150 cm^(-1)and 44580 cm^(-1),from which auto-ionization spectra of the Eu 4f^76p_(1/2)nd states are observed with isolated core excitation method.With all preparations above,the branching ratios from the above auto-ionizing states to different final ionic states and the angular distributions of electrons ejected from these processes are measured systematically.Energy dependence of branching ratios and anisotropy parameters within the auto-ionization spectra are carefully analyzed,followed by a qualitative interpretation.
文摘The paper is devoted to the proof of the uniqueness theorem for solution of the equation for the non-local ionization source in a glow discharge and a hollow cathode in general 3D geometry. The theorem is applied to wide class of electric field configurations, and to the walls of discharge volume, which have a property of incomplete absorption of the electrons. Cathode is regarded as interior singular source, which is placed arbitrarily close to the wall. The existence of solution is considered also. During the proof of the theorem many of useful structure formulae are obtained. Elements of the proof structure, which have arisen, are found to have physical sense. It makes clear physical construction of non-local electron avalanche, which builds a source of ionization in glow discharge at low pressures. Last has decisive significance to understand the hollow cathode discharge configuration and the hollow cathode effect.
基金supported by the Science and Technology Research Project of Gansu Province[20JR5RA555 and145RTSA012]the Natural Science Foundation of Shaanxi Province[2020JQ-541]+1 种基金the National Natural Science Foundation of China[31870851 and 12175289]the Youth Innovation Promotion Association CAS[2021415]
文摘Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237(MLN)and/or p21 depletion by small interfering RNA(si RNA).Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator(FUCCI)system combined with histone H3 phosphorylation at Ser10(p S10 H3)detection.Senescence was assessed using senescence-associated-β-galactosidase(SA-β-Gal),Ki67,andγH2AX staining.Protein expression levels were determined using western blotting.Results Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment.The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells,ultimately leading to senescence in G1.During this process,the p53/p21 pathway is hyperactivated.Accompanying p21 accumulation,Aurora A kinase levels declined sharply.MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.Conclusion Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation,leading to senescence via mitotic skipping.