Metallic tin(Sn)foil is a promising candidate anode for lithium-ion batteries(LIBs)due to its metallurgical processability and high capacity.However,it suffers low initial Coulombic efficiency and inferior cycling sta...Metallic tin(Sn)foil is a promising candidate anode for lithium-ion batteries(LIBs)due to its metallurgical processability and high capacity.However,it suffers low initial Coulombic efficiency and inferior cycling stability due to its uneven alloying/dealloying reactions,large volume change and stress,and fast electrode structural degradation.Herein,we report an undulating LiSn electrode fabricated by a scalable two-step procedure involving mechanical lithography and chemical prelithiation of Sn foil.With the combination of experimental measurements and chemo-mechanical simulations,it was revealed the obtained undulating LiSn/Sn electrode could ensure better mechanical stability due to the pre-swelling state from Sn to Li x Sn and undulating structure of lithography in comparison with plane Sn,homogenize the electrochemical alloying/dealloying reactions due to the activated surface materials,and compensate Li loss during cycling due to the introduction of excess Li from Li_(x)Sn,thus enabling enhanced electrochemical performance.Symmetric cells consisting of undulating LiSn/Sn electrode with an active thickness of∼5 um displayed stable cycling over 1000 h at 1 mA cm^(-2) and 1 mAh cm^(-2) with a low average overpotential of<15 mV.When paired with commercial LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2)(NCM622)cathode with high mass loading of 15.8 mg cm^(-2),the full cell demonstrated a high capacity of 2.4 mAh cm^(-2) and outstanding cycling stability with 84.9% capacity retention at 0.5 C after 100 cycles.This work presents an advanced LiSn electrode with stress-regulation design toward high-performance LIBs,and sheds light on the rational electrode design and processing of other high-capacity lithium alloy anodes.展开更多
A series of Ce-doped MnOx/TiO2 catalysts were prepared by impregnation method and used for catalytic oxidation of NO in the presence of excess O2. The sample with the Ce doping concentration of Ce/Mn=l/3 and calcined ...A series of Ce-doped MnOx/TiO2 catalysts were prepared by impregnation method and used for catalytic oxidation of NO in the presence of excess O2. The sample with the Ce doping concentration of Ce/Mn=l/3 and calcined at 300 ℃ shows a superior activity for NO oxidation to NO2. On Ce(1)Mn(3)Ti catalyst, 58% NO conversion was obtained at 200 ℃ and 85% NO conversion at 250 ℃ with a GHSV of 41000 h-1, which was much higher than that over MnOx/TiO2 catalyst (48% at 250 ℃). Characterization results implied that the higher activity of Ce(1)Mn(3)Ti could be attributed to the enrichment of well-dispersed MnO2 on the surface and the abundance of Mn3+ and Zi3+ species. The addition of Ce into MnO2/TiO2 could improve oxygen storage capacity and facilitate oxygen mobility of the catalyst as shown by PL and ESR, so that its activity for NO oxidation could be enhanced. The effect of H2O and SO2 on the catalyst activity was also investigated.展开更多
Phyllostachys edulis plays an important role in maintaining carbon cycling.We examined the effects of soil properties on organic carbon content in a P.edulis forest on Dagang Mountain,Jiangxi Province,China.Based on c...Phyllostachys edulis plays an important role in maintaining carbon cycling.We examined the effects of soil properties on organic carbon content in a P.edulis forest on Dagang Mountain,Jiangxi Province,China.Based on correlation and stepwise multiple regression analyses,the effects of seven soil factors on organic carbon and their sensitivities to change were studied using path and sensitivity analyses.The results revealed differences in the interconnections and intensities of soil factors on organic carbon.Soil porosity,field capacity,and ammonium nitrogen levels were the main factors affecting organic carbon in the ecosystem.Soil porosity had a strong direct effect on organic carbon content and a strong indirect effect through field capacity.Field capacity and ammonium nitrogen levels mainly affected organic carbon directly.Field capacity,soil porosity,and ammonium nitrogen content,as well as bulk density,b-glucosidase activity,and invertase activity,were sensitive factors.Polyphenol oxidase activity was insensitive.Our study provides a theoretical basis for understanding the effects of soil factors on organic carbon,which can be utilised to improve P.edulis forest management strategies and promote carbon sequestration capacities.展开更多
Objective This study aimed to investigate the effect of radiotherapy on serum immune-associated cells and tumor markers in patients with esophageal cancer.Methods A total of 87 patients with esophageal cancer admitted...Objective This study aimed to investigate the effect of radiotherapy on serum immune-associated cells and tumor markers in patients with esophageal cancer.Methods A total of 87 patients with esophageal cancer admitted to our hospital between October 2016 and July 2020 were selected as the observation group,and all patients received radiotherapy.A total of 87 healthy volunteers who underwent physical examination at our hospital during the same period were selected as the control group in order to compare the changes in serum immune-associated cells and tumor markers between the two groups.Results The levels of carcinoembryonic antigen(CEA),cancer antigen(CA)125,CA72-4,C-terminus of cytokeratin(CYFRA)21-1,and squamous cell carcinoma(SCC)antigen in the observation group before radiotherapy were higher than those in the control group,and the differences were significant(P<0.05).The levels of CEA,CA125,CA72-4,CYFRA21-1,and SCC antigen in the research group after radiotherapy were significantly lower than those before radiotherapy,but were still significantly higher than those in the control group(P<0.05).The levels of CD3+,CD4+,CD4+/CD8+,and natural killer cells in the research group before and after radiotherapy were significantly lower,while the levels of Treg and CD8+cells were significantly higher than those in the control group(P<0.05).The levels of CD3+,CD4+,and CD4+/CD8+cells in the observation group after radiotherapy were lower,while the levels of CD8+cells were significantly higher than those before radiotherapy(P<0.05).Conclusion Radiotherapy can effectively reduce the level of serum tumor markers in patients with esophageal cancer;these antigens and cells can be used as tumor markers of esophageal cancer in order to determine its prognosis.However,radiotherapy has adverse effects on the immune function of the body.The reasons behind this need to be further studied and analyzed.展开更多
The Internet now is a large-scale platform with big data. Finding truth from a huge dataset has attracted extensive attention, which can maintain the quality of data collected by users and provide users with accurate ...The Internet now is a large-scale platform with big data. Finding truth from a huge dataset has attracted extensive attention, which can maintain the quality of data collected by users and provide users with accurate and efficient data. However, current truth finder algorithms are unsatisfying, because of their low accuracy and complication. This paper proposes a truth finder algorithm based on entity attributes (TFAEA). Based on the iterative computation of source reliability and fact accuracy, TFAEA considers the interactive degree among facts and the degree of dependence among sources, to simplify the typical truth finder algorithms. In order to improve the accuracy of them, TFAEA combines the one-way text similarity and the factual conflict to calculate the mutual support degree among facts. Furthermore, TFAEA utilizes the symmetric saturation of data sources to calculate the degree of dependence among sources. The experimental results show that TFAEA is not only more stable, but also more accurate than the typical truth finder algorithms.展开更多
Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor prognosis.Despite that pyrotinib,a new...Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor prognosis.Despite that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance.Therefore,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity.Here,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC.We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice models.This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress.Furthermore,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of BC.Mechanistically,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with ZBTB16.Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC.Together,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.展开更多
Despite the use of many types of chemotherapies for pancreatic cancer, optimal efficacy has not been obtained so far. Pancreatic cancer shows a high incidence of TP53 mutations, inactivating its tumor suppressor activ...Despite the use of many types of chemotherapies for pancreatic cancer, optimal efficacy has not been obtained so far. Pancreatic cancer shows a high incidence of TP53 mutations, inactivating its tumor suppressor activity. In this study, we identified sodium cantharidinate as a novel, potential anti-pancreatic cancer agent that activates p53 function. Sodium cantharidinate reduced the viability of pancreatic cancer cells, including the human primary pancreatic cancer cells, PANC-1, As PC-1, SW1990 and BXPC-3, in a dose-dependent manner. Sodium cantharidinate induced apoptosis and DNA damage of pancreatic cancer cells. Furthermore, proteome-wide sequencing analysis detected a marked perturbation in p53 signaling pathway on PANC-1 cells upon sodium cantharidinate. Consistent with the previous results, sodium cantharidinate treatment decreased Bcl-2 and mitochondrial cytochrome-c protein expression, as well as phosphorylation of MDM2;meanwhile, it increased the levels of cleaved-caspase-3,cleaved-caspase-9, cleaved-PARP, Bax, and phosphorylated p53, thus inducing the apoptosis of pancreatic cancer cells. The p53-activating effect of sodium cantharidinate was strongly abrogated by treatment with TP53-targeting sh RNA. Moreover, sodium cantharidinate inhibited neoplasm growth via the JAK2-STAT3 pathway, which was inhibited by sh RNA-TP53 and triggered by combination with gemcitabine. Combination therapy indicated that sodium cantharidinate and gemcitabine synergistically reduced ex vivo and in vivo growth of pancreatic neoplasm. Further docking studies revealed the different binding fates of sodium cantharidinate to activate wild-type p53 function. Thus, sodium cantharidinate could be a potential agent with promising anti-pancreatic cancer efficacy.展开更多
The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemoki...The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME.In this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.The delivery of plasmid CKb11(pCKb11)by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor tissues.Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.Our study demonstrated a nanotechnology-enabled delivery of pCKb11,that remodeled the immunosuppressive TME,for cancer treatment.展开更多
As one of the important materials,nanocrystalline Au(n-Au)has gained numerous interests in recent decades owing to its unique properties and promising applications.However,most of the current n-Au thin films are suppo...As one of the important materials,nanocrystalline Au(n-Au)has gained numerous interests in recent decades owing to its unique properties and promising applications.However,most of the current n-Au thin films are supported on substrates,limiting the study on their mechanical properties and applications.Therefore,it is urgently desired to develop a new strategy to prepare nAu materials with superior mechanical strength and hardness.Here,a hard n-Au material with an average grain size of~40 nm is prepared by cold-forging of the unique Au nanoribbons(NRBs)with unconventional 4H phase under high pressure.Systematic characterizations reveal the phase transformation from 4H to face-centered cubic(fcc)phase during the cold compression.Impressively,the compressive yield strength and Vickers hardness(HV)of the prepared n-Au material reach~140.2 MPa and~1.0 GPa,which are 4.2 and 2.2 times of the microcrystalline Au foil,respectively.This work demonstrates that the combination of high-pressure cold-forging and the in-situ 4H-to-fcc phase transformation can effectively inhibit the grain growth in the obtained n-Au materials,leading to the formation of novel hard n-Au materials.Our strategy opens up a new avenue for the preparation of nanocrystalline metals with superior mechanical property.展开更多
Influenza viruses continue to cause epidemics worldwide every year.However,due to the lack of an effective assessment for the severity of influenza epidemics,it was extremely difficult to take preventative measures.Da...Influenza viruses continue to cause epidemics worldwide every year.However,due to the lack of an effective assessment for the severity of influenza epidemics,it was extremely difficult to take preventative measures.Data were extracted from infectious diseases reports from 2011–2018.Joinpoint regression model and susceptible-exposed-infectious-recovered model were built to understand the characteristics and processes of the epidemic.The reported incidence of influenza was 1,913,698 from January 2011 to February 2018,with an average-yearly-reported-incidence-rate of 19.21 per 100,000.However,there had been a substantial nationwide epidemic of influenza after September 2017,when the average yearly reported incidence rate was 87.29 per 100,000 and an annual percentage change of 48.1%.The hemagglutinin genes of most influenza A(H1N1 and H3N2)viruses from the period of the epidemic had lower homology to those before August 2017.All the hemagglutinin of the recommended A(H3N2,H1N1)and B(Victoria)viruses for vaccines 2017/2018 had low matches with the epidemic viruses.The basic reproduction number was 1.53.The vaccination benefit was linearly related to vaccination coverage,while the quarantine measure had only significantly benefited when over 60%of the quarantined population.The most severe epidemic of influenza in China since 2011 occurred during the period from September 2017 to February 2018.Compared to quarantine,influenza vaccination is more effective way to prevent influenza,and strategies to increase vaccination coverage should be taken for the prevention of severe epidemics of influenza.展开更多
基金This work is financially supported by the Natural Science Foundation of China (Grant No.51802105,12172143,52002136)China Postdoctoral Science Foun-dation.
文摘Metallic tin(Sn)foil is a promising candidate anode for lithium-ion batteries(LIBs)due to its metallurgical processability and high capacity.However,it suffers low initial Coulombic efficiency and inferior cycling stability due to its uneven alloying/dealloying reactions,large volume change and stress,and fast electrode structural degradation.Herein,we report an undulating LiSn electrode fabricated by a scalable two-step procedure involving mechanical lithography and chemical prelithiation of Sn foil.With the combination of experimental measurements and chemo-mechanical simulations,it was revealed the obtained undulating LiSn/Sn electrode could ensure better mechanical stability due to the pre-swelling state from Sn to Li x Sn and undulating structure of lithography in comparison with plane Sn,homogenize the electrochemical alloying/dealloying reactions due to the activated surface materials,and compensate Li loss during cycling due to the introduction of excess Li from Li_(x)Sn,thus enabling enhanced electrochemical performance.Symmetric cells consisting of undulating LiSn/Sn electrode with an active thickness of∼5 um displayed stable cycling over 1000 h at 1 mA cm^(-2) and 1 mAh cm^(-2) with a low average overpotential of<15 mV.When paired with commercial LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2)(NCM622)cathode with high mass loading of 15.8 mg cm^(-2),the full cell demonstrated a high capacity of 2.4 mAh cm^(-2) and outstanding cycling stability with 84.9% capacity retention at 0.5 C after 100 cycles.This work presents an advanced LiSn electrode with stress-regulation design toward high-performance LIBs,and sheds light on the rational electrode design and processing of other high-capacity lithium alloy anodes.
基金supported by the National Natural Science Foundation of China (Grant No. 51078185)
文摘A series of Ce-doped MnOx/TiO2 catalysts were prepared by impregnation method and used for catalytic oxidation of NO in the presence of excess O2. The sample with the Ce doping concentration of Ce/Mn=l/3 and calcined at 300 ℃ shows a superior activity for NO oxidation to NO2. On Ce(1)Mn(3)Ti catalyst, 58% NO conversion was obtained at 200 ℃ and 85% NO conversion at 250 ℃ with a GHSV of 41000 h-1, which was much higher than that over MnOx/TiO2 catalyst (48% at 250 ℃). Characterization results implied that the higher activity of Ce(1)Mn(3)Ti could be attributed to the enrichment of well-dispersed MnO2 on the surface and the abundance of Mn3+ and Zi3+ species. The addition of Ce into MnO2/TiO2 could improve oxygen storage capacity and facilitate oxygen mobility of the catalyst as shown by PL and ESR, so that its activity for NO oxidation could be enhanced. The effect of H2O and SO2 on the catalyst activity was also investigated.
基金supported by the Science and Technology Basic Work Special(No.2014FY120700)
文摘Phyllostachys edulis plays an important role in maintaining carbon cycling.We examined the effects of soil properties on organic carbon content in a P.edulis forest on Dagang Mountain,Jiangxi Province,China.Based on correlation and stepwise multiple regression analyses,the effects of seven soil factors on organic carbon and their sensitivities to change were studied using path and sensitivity analyses.The results revealed differences in the interconnections and intensities of soil factors on organic carbon.Soil porosity,field capacity,and ammonium nitrogen levels were the main factors affecting organic carbon in the ecosystem.Soil porosity had a strong direct effect on organic carbon content and a strong indirect effect through field capacity.Field capacity and ammonium nitrogen levels mainly affected organic carbon directly.Field capacity,soil porosity,and ammonium nitrogen content,as well as bulk density,b-glucosidase activity,and invertase activity,were sensitive factors.Polyphenol oxidase activity was insensitive.Our study provides a theoretical basis for understanding the effects of soil factors on organic carbon,which can be utilised to improve P.edulis forest management strategies and promote carbon sequestration capacities.
基金Supported by a grant from the National Natural Science Foundation of China(No.81872471)。
文摘Objective This study aimed to investigate the effect of radiotherapy on serum immune-associated cells and tumor markers in patients with esophageal cancer.Methods A total of 87 patients with esophageal cancer admitted to our hospital between October 2016 and July 2020 were selected as the observation group,and all patients received radiotherapy.A total of 87 healthy volunteers who underwent physical examination at our hospital during the same period were selected as the control group in order to compare the changes in serum immune-associated cells and tumor markers between the two groups.Results The levels of carcinoembryonic antigen(CEA),cancer antigen(CA)125,CA72-4,C-terminus of cytokeratin(CYFRA)21-1,and squamous cell carcinoma(SCC)antigen in the observation group before radiotherapy were higher than those in the control group,and the differences were significant(P<0.05).The levels of CEA,CA125,CA72-4,CYFRA21-1,and SCC antigen in the research group after radiotherapy were significantly lower than those before radiotherapy,but were still significantly higher than those in the control group(P<0.05).The levels of CD3+,CD4+,CD4+/CD8+,and natural killer cells in the research group before and after radiotherapy were significantly lower,while the levels of Treg and CD8+cells were significantly higher than those in the control group(P<0.05).The levels of CD3+,CD4+,and CD4+/CD8+cells in the observation group after radiotherapy were lower,while the levels of CD8+cells were significantly higher than those before radiotherapy(P<0.05).Conclusion Radiotherapy can effectively reduce the level of serum tumor markers in patients with esophageal cancer;these antigens and cells can be used as tumor markers of esophageal cancer in order to determine its prognosis.However,radiotherapy has adverse effects on the immune function of the body.The reasons behind this need to be further studied and analyzed.
基金supported by the National Natural Science Foundation of China(61472192)the Scientific and Technological Support Project(Society)of Jiangsu Province(BE2016776)
文摘The Internet now is a large-scale platform with big data. Finding truth from a huge dataset has attracted extensive attention, which can maintain the quality of data collected by users and provide users with accurate and efficient data. However, current truth finder algorithms are unsatisfying, because of their low accuracy and complication. This paper proposes a truth finder algorithm based on entity attributes (TFAEA). Based on the iterative computation of source reliability and fact accuracy, TFAEA considers the interactive degree among facts and the degree of dependence among sources, to simplify the typical truth finder algorithms. In order to improve the accuracy of them, TFAEA combines the one-way text similarity and the factual conflict to calculate the mutual support degree among facts. Furthermore, TFAEA utilizes the symmetric saturation of data sources to calculate the degree of dependence among sources. The experimental results show that TFAEA is not only more stable, but also more accurate than the typical truth finder algorithms.
基金supported by the Sichuan Provincial Department of Science and Technology,International Cooperation in Science and Technology Innovation with Hong Kong,Macao,and Taiwan(2023YFH0095)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21035)+2 种基金Beijing Xislike Clinical Oncology Research Foundation(Y-HR2020MS-1031)Beijing Science and Technology Innovation Medical Development Foundation(KC2021-JF-0167-13)Key Research and Development Program of Xuzhou(KC20115)。
文摘Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor prognosis.Despite that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance.Therefore,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity.Here,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC.We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice models.This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress.Furthermore,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of BC.Mechanistically,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with ZBTB16.Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC.Together,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.
基金supported by the National Key R&D Program of China(2019YFC1711000 to P.L.)the National Natural Science Foundation of China(81772566 to J.L.)+1 种基金in part by the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZCX201820 to X.X.)the"Double First-Class"University Project(CPU2018GF04 to XX)。
文摘Despite the use of many types of chemotherapies for pancreatic cancer, optimal efficacy has not been obtained so far. Pancreatic cancer shows a high incidence of TP53 mutations, inactivating its tumor suppressor activity. In this study, we identified sodium cantharidinate as a novel, potential anti-pancreatic cancer agent that activates p53 function. Sodium cantharidinate reduced the viability of pancreatic cancer cells, including the human primary pancreatic cancer cells, PANC-1, As PC-1, SW1990 and BXPC-3, in a dose-dependent manner. Sodium cantharidinate induced apoptosis and DNA damage of pancreatic cancer cells. Furthermore, proteome-wide sequencing analysis detected a marked perturbation in p53 signaling pathway on PANC-1 cells upon sodium cantharidinate. Consistent with the previous results, sodium cantharidinate treatment decreased Bcl-2 and mitochondrial cytochrome-c protein expression, as well as phosphorylation of MDM2;meanwhile, it increased the levels of cleaved-caspase-3,cleaved-caspase-9, cleaved-PARP, Bax, and phosphorylated p53, thus inducing the apoptosis of pancreatic cancer cells. The p53-activating effect of sodium cantharidinate was strongly abrogated by treatment with TP53-targeting sh RNA. Moreover, sodium cantharidinate inhibited neoplasm growth via the JAK2-STAT3 pathway, which was inhibited by sh RNA-TP53 and triggered by combination with gemcitabine. Combination therapy indicated that sodium cantharidinate and gemcitabine synergistically reduced ex vivo and in vivo growth of pancreatic neoplasm. Further docking studies revealed the different binding fates of sodium cantharidinate to activate wild-type p53 function. Thus, sodium cantharidinate could be a potential agent with promising anti-pancreatic cancer efficacy.
基金the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX09201018)Sichuan Science and Technology Program(No.2019YFS0089,2019YFS0340 and 2020YFS0217)+4 种基金the China Postdoctoral Science Foundation(No.2020M680150)full-time postdoctoral research and development fund of Sichuan University(No.20826041D4048)the full-time postdoctoral research and development fund of West China Hospital of Sichuan University(No.2020HXBH059 and No.2020HXBH002)1·3·5 project of excellent development of discipline of West China Hospital of Sichuan University(No.ZYYC21005)the Natural Science Foundation Youth Project of Jiangsu Province(BK20190989).
文摘The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME.In this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.The delivery of plasmid CKb11(pCKb11)by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor tissues.Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.Our study demonstrated a nanotechnology-enabled delivery of pCKb11,that remodeled the immunosuppressive TME,for cancer treatment.
基金supported by the National Natural Science Foundation of China(Nos.52090020,51722209,and 51525205)the National Key Research and Development Program of China(No.2018YFA0305900)+3 种基金Z.S.Z.acknowledges the NSF for Distinguished Young Scholars of Hebei Province of China(No.E2018203349)M.D.M.acknowledges the China Postdoctoral Science Foundation(No.2021M691051)Z.X.F.and H.Z.thank the support from ITC via Hong Kong Branch of National Precious Metals Material Engineering Research Center(NPMM),the Start-Up Grants(Nos.9380100,9610480,and 7200651)grants(Nos.9610478,1886921,7020013,and 7005512)from City University of Hong Kong.
文摘As one of the important materials,nanocrystalline Au(n-Au)has gained numerous interests in recent decades owing to its unique properties and promising applications.However,most of the current n-Au thin films are supported on substrates,limiting the study on their mechanical properties and applications.Therefore,it is urgently desired to develop a new strategy to prepare nAu materials with superior mechanical strength and hardness.Here,a hard n-Au material with an average grain size of~40 nm is prepared by cold-forging of the unique Au nanoribbons(NRBs)with unconventional 4H phase under high pressure.Systematic characterizations reveal the phase transformation from 4H to face-centered cubic(fcc)phase during the cold compression.Impressively,the compressive yield strength and Vickers hardness(HV)of the prepared n-Au material reach~140.2 MPa and~1.0 GPa,which are 4.2 and 2.2 times of the microcrystalline Au foil,respectively.This work demonstrates that the combination of high-pressure cold-forging and the in-situ 4H-to-fcc phase transformation can effectively inhibit the grain growth in the obtained n-Au materials,leading to the formation of novel hard n-Au materials.Our strategy opens up a new avenue for the preparation of nanocrystalline metals with superior mechanical property.
基金supported by grants from the National Natural Science Foundation of China(81672005,81001271)the Key Joint Project for Data Center of the National Natural Science Foundation of China(U1611264)+1 种基金the Mega-Project of National Science and Technology of China(2018ZX10715014002,2014ZX10004008,2013ZX10004901 and 2013ZX10004904)the Fundamental Research Funds for the Central Universities。
文摘Influenza viruses continue to cause epidemics worldwide every year.However,due to the lack of an effective assessment for the severity of influenza epidemics,it was extremely difficult to take preventative measures.Data were extracted from infectious diseases reports from 2011–2018.Joinpoint regression model and susceptible-exposed-infectious-recovered model were built to understand the characteristics and processes of the epidemic.The reported incidence of influenza was 1,913,698 from January 2011 to February 2018,with an average-yearly-reported-incidence-rate of 19.21 per 100,000.However,there had been a substantial nationwide epidemic of influenza after September 2017,when the average yearly reported incidence rate was 87.29 per 100,000 and an annual percentage change of 48.1%.The hemagglutinin genes of most influenza A(H1N1 and H3N2)viruses from the period of the epidemic had lower homology to those before August 2017.All the hemagglutinin of the recommended A(H3N2,H1N1)and B(Victoria)viruses for vaccines 2017/2018 had low matches with the epidemic viruses.The basic reproduction number was 1.53.The vaccination benefit was linearly related to vaccination coverage,while the quarantine measure had only significantly benefited when over 60%of the quarantined population.The most severe epidemic of influenza in China since 2011 occurred during the period from September 2017 to February 2018.Compared to quarantine,influenza vaccination is more effective way to prevent influenza,and strategies to increase vaccination coverage should be taken for the prevention of severe epidemics of influenza.