A subset D■V(G)in a graph G is a dominating set if every vertex in V(G)I D is adjacent to at least one vertex of S.A subset S■V(G)in a graph G is a 2-independent set if△(G[S])<2.The 2-independence numberα2(G)is...A subset D■V(G)in a graph G is a dominating set if every vertex in V(G)I D is adjacent to at least one vertex of S.A subset S■V(G)in a graph G is a 2-independent set if△(G[S])<2.The 2-independence numberα2(G)is the order of a largest 2-independent set in G.Further,a subset D■V(G)in a graph G is a 2-independent dominating set if D is both dominating and 2-independent.The 2-independent domination number i^(2)(G)is the order of a smallest 2-independent dominating set in G.In this paper,we characterize all trees T of order n with i^(2)(T)=n/2.Moreover,we prove that for any tree T of order n≥2,i^(2)(T)≤2/3α2(T),and this bound is sharp.展开更多
AIM: To investigate the effect of oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24 on hepatocellular carcinoma (HCC) cell lines and normal liver cell line. METHODS: HCC cell lines (HepG2...AIM: To investigate the effect of oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24 on hepatocellular carcinoma (HCC) cell lines and normal liver cell line. METHODS: HCC cell lines (HepG2, Hep3B and MHCC97L) and normal liver cell line (L02) with a different p53 status were infected with SG600-IL24 and Ad.IL-24, respectively. Melanoma differentiation-associated (MDA)-7/interleukin (IL)-24 mRNA and protein expressions in infected cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), enzymelinked immunosorbent assay (ELISA), and Western blotting, respectively. Apoptosis of HCC cells and normal liver cells was detected by cytometric assay with Hoechst33258 staining. 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay was used to investigate proliferation of HCC cells and normal liver cells, and cell cycle was assayed by flow cytometry. RESULTS: RT-PCR, ELISA and Western blotting showed that the exogenous MDA-7/IL-24 gene was highly expressed in cells infected with SG600-IL24. MTT indicated that SG600-IL24 could suppress the growth of HepG2, Hep3B, MHCC97L, with an inhibition rate of 75% ± 2.5%, 85% ± 2.0%, 72% ± 1.8%, respectively (P < 0.01), promote the apoptosis of HepG2, Hep3B, MHCC97L, with an apoptosis rate of 56.59% ± 4.0%, 78.36% ± 3.5%, 43.39% ± 2.5%, respectively (P < 0.01), and block the HCC cell lines in the G2/M phase with a blocking rate of 35.4% ± 4.2%, 47.3% ± 6.2%, 42% ± 5.0%, respectively (P < 0.01) but not the normal liver cell line in a p53-independent manner. CONCLUSION: SG600-IL24 can selectively suppress the proliferation and apoptosis of HCC cell lines in vitro but not normal liver cell line L02 in a p53-independent manner. Compared with Ad.IL-24, SG600-IL24 can significantly enhance the antitumor activity in HCC cell lines.展开更多
Summary Vacuolar trafficking routes and their regu- lators have recently drawn lots of attention in plant cell biology. A recent study reported the discovery of a plant-specific vacuolar trafficking route, i.e., a dir...Summary Vacuolar trafficking routes and their regu- lators have recently drawn lots of attention in plant cell biology. A recent study reported the discovery of a plant-specific vacuolar trafficking route, i.e., a direct ER- to-vacuole route, through analysis of VHA-a3 subcellular targeting, a key component for the tonoplast V- ATPases. Our recent findings showed that VHA-a3 targets to the tonoplast through a Rab5-mediated but Rab7-independent pathway, shedding new lights on the unconventional vacuolar trafficking route in plant cells.展开更多
OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation(LTP)and cognitive impairment induced by stress or corticosterone.However,other studies showed t...OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation(LTP)and cognitive impairment induced by stress or corticosterone.However,other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment.The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms.METHODS Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS)to induce LTP impairment.NMDA receptor antagonists and agonists were administrated by icv.RESULTS Hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice.Corticosterone increased the glutamate level in hippocampal tissues,neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP,while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone,suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticosterone.Further results showed that the level of D-serine and its precursor L-serine did not change.D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1(ASC-1)in the cell membrane was decreased and increasing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticosterone.CONCLUSION Taken together,this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction,which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.展开更多
Photodynamic therapy(PDT)usually shows limited efficacy in solid tumors since traditional PDT is O_(2)^(-)dependent while solid tumors are inherently hypoxic.In addition,hypoxic tumor cells possess antiapoptotic pathw...Photodynamic therapy(PDT)usually shows limited efficacy in solid tumors since traditional PDT is O_(2)^(-)dependent while solid tumors are inherently hypoxic.In addition,hypoxic tumor cells possess antiapoptotic pathways that resist PDT-induced apoptosis.Therefore,developing photosensitizers(PSs)that show low O_(2)^(-)dependency and can induce nonapoptotic cell death pathways is critically needed.Herein,a series of Ru(II)polypyridine complex-based PSs,RuNMe,RuH,and RuCN,were synthesized,and their applications against hypoxic tumor cells through PDT were investigated.All three complexes showthe ability to generate the superoxide anion radical(·O_(2)^(-)),which is the type I photoreaction and less O_(2)^(-)dependent.RuNMe shows the best PDT performance against MCF-7 cells and three-dimensional multicellular spheroids,due to its higher cellular uptake and more reactive oxygen species generation.More importantly,RuNMe-incubated MCF-7 cells show photoinduced ferroptosis as evidenced by glutathione peroxidase 4 downregulation and lipid peroxide accumulation.This work not only develops a novel ferroptosis-inducing Ru(II)complex with the type I PDT process but also offers an effective strategy to solve tumor hypoxia in PDT.展开更多
Let G be a graph and S a subset of vertices of G. In the paper we give a local condition on cycles in G dominating all vertices of S with large sums. We also derive some consequences on local hamiltonian conditions.
This paper develops a framework to deal with the unconditional superclose analysis of nonlinear parabolic equation.Taking the finite dement pair Q11/Q01×Q10 as an example, a new mixed finite element method (FEM)i...This paper develops a framework to deal with the unconditional superclose analysis of nonlinear parabolic equation.Taking the finite dement pair Q11/Q01×Q10 as an example, a new mixed finite element method (FEM)is established and the r-independent superclose results of the original variable u in Hi-norm and the flux variable q=-a(u)■u in L^2- norm are deduced (τ is the temporal partition parameter).A key to our analysis is all error splitting technique,with which the time-discrete and the spatial-discrete systems are constructed,respectively.For the first system,tile boundedness of the temporal errors are obtained.For the second system,the spatial superclose results are presented unconditionally.while the previous literature always only obtain the convergent estimates or require certain time step conditions.Finally,some numerical results are provided to confirm the theoretical analysis,and show the efficiency of the proposed method.展开更多
Overexpression of the MDM2 oncogene and mutations in the p53 tumor suppressor commonly occur in hepatocellular carcinoma(HCC)and are associated with increased mortality due to this disease.Inhibiting MDM2 has been dem...Overexpression of the MDM2 oncogene and mutations in the p53 tumor suppressor commonly occur in hepatocellular carcinoma(HCC)and are associated with increased mortality due to this disease.Inhibiting MDM2 has been demonstrated to be a valid approach for the treatment of HCC.However,most of the MDM2 inhibitors evaluated to date have been designed to block the MDM2 and p53 binding,and have limited efficacy against tumors with mutant or deficient p53.In the present study,we developed a novel MDM2 inhibitor(termed SP141)that has direct effects on MDM2 and exerts anti-HCC activity independent of the p53 status of the cancer cells.We demonstrate that SP141 inhibits cell growth and prevents cell migration and invasion,independent of p53.Mechanistically,SP141 directly binds the MDM2 protein and promotes MDM2 degradation.The inhibition of MDM2 by SP141 also increases the sensitivity of HCC cells to sorafenib.In addition,in orthotopic and patient-derived xenograft models,SP141 inhibits MDM2 expression and suppresses tumor growth and metastasis,without any host toxicity.Furthermore,the inhibition of MDM2 by SP141 is essential for its anti-HCC activities.These results provide support for the further development of SP141 as a lead candidate for the treatment of HCC.展开更多
基金the National Natural Science Foundation of China(No.12061073).
文摘A subset D■V(G)in a graph G is a dominating set if every vertex in V(G)I D is adjacent to at least one vertex of S.A subset S■V(G)in a graph G is a 2-independent set if△(G[S])<2.The 2-independence numberα2(G)is the order of a largest 2-independent set in G.Further,a subset D■V(G)in a graph G is a 2-independent dominating set if D is both dominating and 2-independent.The 2-independent domination number i^(2)(G)is the order of a smallest 2-independent dominating set in G.In this paper,we characterize all trees T of order n with i^(2)(T)=n/2.Moreover,we prove that for any tree T of order n≥2,i^(2)(T)≤2/3α2(T),and this bound is sharp.
基金Supported by National Natural Science Foundation of China,No. 30872510Natural Science Foundation of Hubei Province,No. 2008CDB127
文摘AIM: To investigate the effect of oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24 on hepatocellular carcinoma (HCC) cell lines and normal liver cell line. METHODS: HCC cell lines (HepG2, Hep3B and MHCC97L) and normal liver cell line (L02) with a different p53 status were infected with SG600-IL24 and Ad.IL-24, respectively. Melanoma differentiation-associated (MDA)-7/interleukin (IL)-24 mRNA and protein expressions in infected cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), enzymelinked immunosorbent assay (ELISA), and Western blotting, respectively. Apoptosis of HCC cells and normal liver cells was detected by cytometric assay with Hoechst33258 staining. 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay was used to investigate proliferation of HCC cells and normal liver cells, and cell cycle was assayed by flow cytometry. RESULTS: RT-PCR, ELISA and Western blotting showed that the exogenous MDA-7/IL-24 gene was highly expressed in cells infected with SG600-IL24. MTT indicated that SG600-IL24 could suppress the growth of HepG2, Hep3B, MHCC97L, with an inhibition rate of 75% ± 2.5%, 85% ± 2.0%, 72% ± 1.8%, respectively (P < 0.01), promote the apoptosis of HepG2, Hep3B, MHCC97L, with an apoptosis rate of 56.59% ± 4.0%, 78.36% ± 3.5%, 43.39% ± 2.5%, respectively (P < 0.01), and block the HCC cell lines in the G2/M phase with a blocking rate of 35.4% ± 4.2%, 47.3% ± 6.2%, 42% ± 5.0%, respectively (P < 0.01) but not the normal liver cell line in a p53-independent manner. CONCLUSION: SG600-IL24 can selectively suppress the proliferation and apoptosis of HCC cell lines in vitro but not normal liver cell line L02 in a p53-independent manner. Compared with Ad.IL-24, SG600-IL24 can significantly enhance the antitumor activity in HCC cell lines.
基金supported by Major Research Plan(2013CB945102) from the Ministry of Science,Technology of ChinaNational Natural Science Foundation of China(31261160490 to Y.Z.)Natural Science Foundation of Shandong Province(ZR2014CM027 to S.L.)
文摘Summary Vacuolar trafficking routes and their regu- lators have recently drawn lots of attention in plant cell biology. A recent study reported the discovery of a plant-specific vacuolar trafficking route, i.e., a direct ER- to-vacuole route, through analysis of VHA-a3 subcellular targeting, a key component for the tonoplast V- ATPases. Our recent findings showed that VHA-a3 targets to the tonoplast through a Rab5-mediated but Rab7-independent pathway, shedding new lights on the unconventional vacuolar trafficking route in plant cells.
文摘OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation(LTP)and cognitive impairment induced by stress or corticosterone.However,other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment.The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms.METHODS Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS)to induce LTP impairment.NMDA receptor antagonists and agonists were administrated by icv.RESULTS Hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice.Corticosterone increased the glutamate level in hippocampal tissues,neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP,while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone,suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticosterone.Further results showed that the level of D-serine and its precursor L-serine did not change.D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1(ASC-1)in the cell membrane was decreased and increasing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticosterone.CONCLUSION Taken together,this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction,which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.
基金This work was financially supported by the National Natural Science Foundation of China(grant nos.22122701,21731004,91953201,92153303,21977044,and 21907050)the Natural Science Foundation of Jiangsu Province(grant nos.BK20202004 and BK20190282)the Excellent Research Program of Nanjing University(grant no.ZYJH004).
文摘Photodynamic therapy(PDT)usually shows limited efficacy in solid tumors since traditional PDT is O_(2)^(-)dependent while solid tumors are inherently hypoxic.In addition,hypoxic tumor cells possess antiapoptotic pathways that resist PDT-induced apoptosis.Therefore,developing photosensitizers(PSs)that show low O_(2)^(-)dependency and can induce nonapoptotic cell death pathways is critically needed.Herein,a series of Ru(II)polypyridine complex-based PSs,RuNMe,RuH,and RuCN,were synthesized,and their applications against hypoxic tumor cells through PDT were investigated.All three complexes showthe ability to generate the superoxide anion radical(·O_(2)^(-)),which is the type I photoreaction and less O_(2)^(-)dependent.RuNMe shows the best PDT performance against MCF-7 cells and three-dimensional multicellular spheroids,due to its higher cellular uptake and more reactive oxygen species generation.More importantly,RuNMe-incubated MCF-7 cells show photoinduced ferroptosis as evidenced by glutathione peroxidase 4 downregulation and lipid peroxide accumulation.This work not only develops a novel ferroptosis-inducing Ru(II)complex with the type I PDT process but also offers an effective strategy to solve tumor hypoxia in PDT.
文摘Let G be a graph and S a subset of vertices of G. In the paper we give a local condition on cycles in G dominating all vertices of S with large sums. We also derive some consequences on local hamiltonian conditions.
基金Natural Science Foundation of China (Grant Nos.11671369,11271340).
文摘This paper develops a framework to deal with the unconditional superclose analysis of nonlinear parabolic equation.Taking the finite dement pair Q11/Q01×Q10 as an example, a new mixed finite element method (FEM)is established and the r-independent superclose results of the original variable u in Hi-norm and the flux variable q=-a(u)■u in L^2- norm are deduced (τ is the temporal partition parameter).A key to our analysis is all error splitting technique,with which the time-discrete and the spatial-discrete systems are constructed,respectively.For the first system,tile boundedness of the temporal errors are obtained.For the second system,the spatial superclose results are presented unconditionally.while the previous literature always only obtain the convergent estimates or require certain time step conditions.Finally,some numerical results are provided to confirm the theoretical analysis,and show the efficiency of the proposed method.
基金W.W. and R.Z. were partially supported by National Institutesof Health (NIH)/National Cancer Institute grants(R01 CA186662 and R01CA214019)W.W. and R.Z. were alsosupported by American Cancer Society (ACS) grant RSG-15-009-01-CDD. R.Z. was also supported by funds for Robert L.Boblitt Endowed Professor in Drug Discovery and researchfunds from College of Pharmacy and University of Houston.J.C., J.F., and X-R. Y. were supported by grants from theNational Natural Science Foundation of China (No.81272389, 81472674, 81502486). The content of this reportis solely the responsibility of the authors, and does notnecessarily represent the official views of the National Institutesof Health or other funding agencies.
文摘Overexpression of the MDM2 oncogene and mutations in the p53 tumor suppressor commonly occur in hepatocellular carcinoma(HCC)and are associated with increased mortality due to this disease.Inhibiting MDM2 has been demonstrated to be a valid approach for the treatment of HCC.However,most of the MDM2 inhibitors evaluated to date have been designed to block the MDM2 and p53 binding,and have limited efficacy against tumors with mutant or deficient p53.In the present study,we developed a novel MDM2 inhibitor(termed SP141)that has direct effects on MDM2 and exerts anti-HCC activity independent of the p53 status of the cancer cells.We demonstrate that SP141 inhibits cell growth and prevents cell migration and invasion,independent of p53.Mechanistically,SP141 directly binds the MDM2 protein and promotes MDM2 degradation.The inhibition of MDM2 by SP141 also increases the sensitivity of HCC cells to sorafenib.In addition,in orthotopic and patient-derived xenograft models,SP141 inhibits MDM2 expression and suppresses tumor growth and metastasis,without any host toxicity.Furthermore,the inhibition of MDM2 by SP141 is essential for its anti-HCC activities.These results provide support for the further development of SP141 as a lead candidate for the treatment of HCC.