Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the domi...Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation.The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16(wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4^(+) T lymphocytes, and the Th1(IFN-γ) and Th2(IL-4 and IL-6)cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.展开更多
Background:Preeclampsia(PE),characterized by hypertension and proteinuria,leads to serious maternal and infant complications.Uridine-cytidine kinase 2(UCK2)belongs to the UCK family,a class of enzymes that catalyzes t...Background:Preeclampsia(PE),characterized by hypertension and proteinuria,leads to serious maternal and infant complications.Uridine-cytidine kinase 2(UCK2)belongs to the UCK family,a class of enzymes that catalyzes the conversion of uridine and cytidine to monophosphate form.However,the role of UCK2 in PE has not been reported.Methods:The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model.Through forced up-regulation or down-regulation of UCK2 in vitro,we examined the effects of UCK2 on the proliferation,apoptosis,migration,and invasion of trophoblast cells.Stattic,the inhibitor of STAT3 pathway,was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 in trophoblast cells.Results:The present study found that UCK2 showed low expression in the placenta of PE patients and PE mouse model.MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)and flow cytometry assays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells,while the silence of UCK2 suppressed cell proliferation.Besides,flow cytometry and TdT-mediated dUTP Nick-End Labeling assays demonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells.The wound healing and transwell assays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpression of UCK2 and were blocked by the silence of UCK2.Furthermore,the expression of phosphorylated STAT3 was increased with the upregulation of UCK2 and decreased with the inhibition of UCK2.When the STAT3 pathway was blocked by its inhibitor stattic,the promotion effects of UCK2 on trophoblast cells were suppressed.Conclusion:UCK2 promotes the proliferation,migration,and invasion of trophoblast cells,and these effects may be partly mediated by the activation of the STAT3 pathway.展开更多
A hierarchical superhydrophobic Al-Li layered double hydroxide(LDH)films with different Li^(+)/Al^(3+)molar ratios of 1:1,1:2,2:1,p H value of 11.5 and reaction temperature of 125°C,have been fabricated on the su...A hierarchical superhydrophobic Al-Li layered double hydroxide(LDH)films with different Li^(+)/Al^(3+)molar ratios of 1:1,1:2,2:1,p H value of 11.5 and reaction temperature of 125°C,have been fabricated on the surface of Mg-5Li-1Al(LA51)alloys by hydrothermal method following the characteristics of controllable cation structure and exchangeable anion between layers.The properties of the films were investigated by X-ray diffractometer(XRD),scanning electron microscope(SEM)and energy dispersive spectrometer(EDS).XRD and SEM results indicate that the Al-Li LDH films are successfully prepared on LA51 alloys.The contact angle(CA)was measured to be about100.7°,indicating that the surface wettability of the film converted from hydrophilic to hydrophobic by surface modification.The corrosion resistance of Al-Li LDH films was evaluated by Tafel polarization curve and electrochemical impedance spectroscopy(EIS).Surprisingly,Tafel polarization curve and EIS test reveal that the Al-Li LDH films prepared at the molar ratio of Li^(+)/Al^(3+)1:2,p H 11.5 and temperature125°C have better corrosion resistance in 0.1 M Na Cl neutral solution.In addition,the formation mechanism and corrosion mechanism of the films on the surface of LA51 alloy are also proposed.It provides innovative synthetic materials and novel design ideas for the preparation of high-efficiency anti-corrosion coatings on LA51 alloys,whose application can be extended in industrial fields.展开更多
In this study,multivariate analysis methods,including a principal component analysis(PCA)and partial least square(PLS)analysis,were applied to reveal the inner relationship of the key variables in the process of H_(2)...In this study,multivariate analysis methods,including a principal component analysis(PCA)and partial least square(PLS)analysis,were applied to reveal the inner relationship of the key variables in the process of H_(2)O_(2)-assisted Na_(2)CO_(3)(HSC)pretreatment of corn stover.A total of 120 pretreatment experiments were implemented at the lab scale under different conditions by varying the particle size of the corn stover and process variables.The results showed that the Na_(2)CO_(3) dosage and pretreatment temperature had a strong influence on lignin removal,whereas pulp refining instrument(PFI)refining and Na_(2)CO_(3) dosage played positive roles in the final total sugar yield.Furthermore,it was found that pretreatment conditions had a more significant impact on the amelioration of pretreatment effectiveness compared with the properties of raw corn stover.In addition,a prediction of the effectiveness of the corn stover HSC pretreatment based on a PLS analysis was conducted for the first time,and the test results of the predictability based on additional pretreatment experiments proved that the developed PLS model achieved a good predictive performance(particularly for the final total sugar yield),indicating that the developed PLS model can be used to predict the effectiveness of HSC pretreatment.Therefore,multivariate analysis can be potentially used to monitor and control the pretreatment process in future large-scale biorefinery applications.展开更多
Bacillus subtilis HAS is a biocontrol strain with better inhibitory effect on Sporisorium scitaminea Sydow. In order to further understand its action range,with fungal pathogens in sugarcane production as targets,conf...Bacillus subtilis HAS is a biocontrol strain with better inhibitory effect on Sporisorium scitaminea Sydow. In order to further understand its action range,with fungal pathogens in sugarcane production as targets,confrontation tests and tests of inhibitory effect of secondary metabolites on growth of pathogens were carried out. The results showed that B. subtilis HAS not only had better inhibitory effect on S. Scitaminea,but also inhibited the growth of various fungal pathogens in sugarcane production. The inhibitory effect was the best on Ceratocystis adiposum,Thielaviopsis paradoxa,Fusarium moniliforme and Colletotrichum fuleatum,which was reflected by the radius of inhibitory zone over 10 mm. The inhibitory rates of the secondary metabolites were about 70%. It indicates that B. subtilis HAS has wide antifungal property,providing reference for further application of this strain.展开更多
Choline acetyltransferase(ChAT)-positive neurons in neural stem cell(NSC)niches can evoke adult neurogenesis(AN)and restore impaired brain function after injury,such as acute ischemic stroke(AIS).However,the relevant ...Choline acetyltransferase(ChAT)-positive neurons in neural stem cell(NSC)niches can evoke adult neurogenesis(AN)and restore impaired brain function after injury,such as acute ischemic stroke(AIS).However,the relevant mechanism by which ChAT+neurons develop in NSC niches is poorly understood.Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1(DDAH1),a hydrolase for asymmetric NG,NG-dimethylarginine(ADMA),regulated genes responsible for the synthesis and transportation of acetylcholine(ACh)(Chat,Slc5a7 and Slc18a3)after stroke insult.The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT,possibly through hypoxia-inducible factor 1α(HIF-1α).KC7F2,an inhibitor of HIF-1α,abolished DDAH1-induced ChAT expression and suppressed neurogenesis.As expected,DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity.By comparing the results among Ddah1 general knockout(KO)mice,transgenic(TG)mice and wild-type(WT)mice,we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone(SGZ)under ischemic insult.As a result,DDAH1 may promote cognitive and motor function recovery against stroke impairment,while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.展开更多
In the past decade, significant knowledge has accumulated regarding gibberellin （GA） signal transductlon In rice as a result of studies using multiple approaches, particularly molecular genetics. The present review ...In the past decade, significant knowledge has accumulated regarding gibberellin （GA） signal transductlon In rice as a result of studies using multiple approaches, particularly molecular genetics. The present review highlights the recent developments In the identification of GA signaling pathway components, the discovery of GA-Induced destructlon of GA signaling repressor （DELLA protein）, and the possible mechanism underlying the regulation of GA- responsive gene expression in rice.展开更多
Although targeted therapy has been extensively investigated for breast cancers,a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers.Mammaglobin-A(Mam-A),whi...Although targeted therapy has been extensively investigated for breast cancers,a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers.Mammaglobin-A(Mam-A),which is overexpressed in most breast carcinomas,has been proposed as a promising target.However,the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study.Here,seven potential epitopes of Mam-A were disclosed,and a unique epitope was then identified in most types of breast cancers,despite the genotypic heterogeneity.With phage display technology,the epitope was determined to be N-terminal amino acids 42–51 of Mam-A(N42–51).Then,the N42–51 epitope-specific monoclonal antibody,mAb785,was conjugated to poly lactic-co-glycolic acid(PLGA)nanoparticles loaded with therapeutic agents,thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers.The computer simulation of the N42–51 epitope and the mAb785 structures,as well as their interactions,further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.展开更多
基金supported by the National Key Research and Development Program of China (2022YFD1800604)the China Agricultural Research System (CARS-41)the Heilongjiang Touyan Innovation Team Program of China
文摘Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation.The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16(wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4^(+) T lymphocytes, and the Th1(IFN-γ) and Th2(IL-4 and IL-6)cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.
基金supported by“Heart Health Research Fund,”Special Fund for Cardiovascular Disease Development of China,China International Medical Foundation(Grant No.Z-2019-42-1908-3),Tianjin Key Medical Discipline(Specialty)Construction Project,and the Young Talents Training Program of Tianjin First Central Hospital.
文摘Background:Preeclampsia(PE),characterized by hypertension and proteinuria,leads to serious maternal and infant complications.Uridine-cytidine kinase 2(UCK2)belongs to the UCK family,a class of enzymes that catalyzes the conversion of uridine and cytidine to monophosphate form.However,the role of UCK2 in PE has not been reported.Methods:The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model.Through forced up-regulation or down-regulation of UCK2 in vitro,we examined the effects of UCK2 on the proliferation,apoptosis,migration,and invasion of trophoblast cells.Stattic,the inhibitor of STAT3 pathway,was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 in trophoblast cells.Results:The present study found that UCK2 showed low expression in the placenta of PE patients and PE mouse model.MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)and flow cytometry assays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells,while the silence of UCK2 suppressed cell proliferation.Besides,flow cytometry and TdT-mediated dUTP Nick-End Labeling assays demonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells.The wound healing and transwell assays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpression of UCK2 and were blocked by the silence of UCK2.Furthermore,the expression of phosphorylated STAT3 was increased with the upregulation of UCK2 and decreased with the inhibition of UCK2.When the STAT3 pathway was blocked by its inhibitor stattic,the promotion effects of UCK2 on trophoblast cells were suppressed.Conclusion:UCK2 promotes the proliferation,migration,and invasion of trophoblast cells,and these effects may be partly mediated by the activation of the STAT3 pathway.
基金the financial support of the Natural Science Foundation of Inner Mongolia Autonomous Region(Grant NO.2019MS05037)Chunhui Program of Ministry of Education of China(Grant NO.CHJH2018)+5 种基金Key Technology Project of Inner Mongolia Autonomous Region(Grant NO.2021GG0094)Supported by Youth project of science and technology research program of Chongqing Education Commission of China(KJ201903136636560)provided by the National Natural Science Foundation of China(Grant No.51908092),Projects(No.2020CDJXZ001 and 2021CDJJMRH-005)the Fundamental Research Funds for the Central Universitiesthe Joint Funds of the National Natural Science Foundation of China-Guangdong(Grant No.U1801254)the project funded by Chongqing Special Postdoctoral Science Foundation(Xm T2018043)
文摘A hierarchical superhydrophobic Al-Li layered double hydroxide(LDH)films with different Li^(+)/Al^(3+)molar ratios of 1:1,1:2,2:1,p H value of 11.5 and reaction temperature of 125°C,have been fabricated on the surface of Mg-5Li-1Al(LA51)alloys by hydrothermal method following the characteristics of controllable cation structure and exchangeable anion between layers.The properties of the films were investigated by X-ray diffractometer(XRD),scanning electron microscope(SEM)and energy dispersive spectrometer(EDS).XRD and SEM results indicate that the Al-Li LDH films are successfully prepared on LA51 alloys.The contact angle(CA)was measured to be about100.7°,indicating that the surface wettability of the film converted from hydrophilic to hydrophobic by surface modification.The corrosion resistance of Al-Li LDH films was evaluated by Tafel polarization curve and electrochemical impedance spectroscopy(EIS).Surprisingly,Tafel polarization curve and EIS test reveal that the Al-Li LDH films prepared at the molar ratio of Li^(+)/Al^(3+)1:2,p H 11.5 and temperature125°C have better corrosion resistance in 0.1 M Na Cl neutral solution.In addition,the formation mechanism and corrosion mechanism of the films on the surface of LA51 alloy are also proposed.It provides innovative synthetic materials and novel design ideas for the preparation of high-efficiency anti-corrosion coatings on LA51 alloys,whose application can be extended in industrial fields.
基金This work was financially supported by the National Natural Science Foundation of China(No.31870568)Shandong Provincial Natural Science Foundation for Distinguished Young Scholars(China)(No.ZR2019JQ10)+1 种基金the Major Program of the Shandong Province Natural Science Foundation(No.ZR2018ZB0208)the"Transformational Technologies for Clean Energy and Demonstration"Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA21060201).
文摘In this study,multivariate analysis methods,including a principal component analysis(PCA)and partial least square(PLS)analysis,were applied to reveal the inner relationship of the key variables in the process of H_(2)O_(2)-assisted Na_(2)CO_(3)(HSC)pretreatment of corn stover.A total of 120 pretreatment experiments were implemented at the lab scale under different conditions by varying the particle size of the corn stover and process variables.The results showed that the Na_(2)CO_(3) dosage and pretreatment temperature had a strong influence on lignin removal,whereas pulp refining instrument(PFI)refining and Na_(2)CO_(3) dosage played positive roles in the final total sugar yield.Furthermore,it was found that pretreatment conditions had a more significant impact on the amelioration of pretreatment effectiveness compared with the properties of raw corn stover.In addition,a prediction of the effectiveness of the corn stover HSC pretreatment based on a PLS analysis was conducted for the first time,and the test results of the predictability based on additional pretreatment experiments proved that the developed PLS model achieved a good predictive performance(particularly for the final total sugar yield),indicating that the developed PLS model can be used to predict the effectiveness of HSC pretreatment.Therefore,multivariate analysis can be potentially used to monitor and control the pretreatment process in future large-scale biorefinery applications.
基金Supported by Natural Science Foundation of China(31471555)Special Fund for Basic Scientific Research of Central Nonprofit Research Institutes(1630052016010)National Agro-Industry(Sugar Industry)Technology Research System(CARS-170301)
文摘Bacillus subtilis HAS is a biocontrol strain with better inhibitory effect on Sporisorium scitaminea Sydow. In order to further understand its action range,with fungal pathogens in sugarcane production as targets,confrontation tests and tests of inhibitory effect of secondary metabolites on growth of pathogens were carried out. The results showed that B. subtilis HAS not only had better inhibitory effect on S. Scitaminea,but also inhibited the growth of various fungal pathogens in sugarcane production. The inhibitory effect was the best on Ceratocystis adiposum,Thielaviopsis paradoxa,Fusarium moniliforme and Colletotrichum fuleatum,which was reflected by the radius of inhibitory zone over 10 mm. The inhibitory rates of the secondary metabolites were about 70%. It indicates that B. subtilis HAS has wide antifungal property,providing reference for further application of this strain.
基金This work was supported by the National Natural Science Foundation of China(32171237,82070250,82171301,82370275,32071126)Beijing Natural Science Foundation(7222010)the Fundamental Research Funds for the Central Universities.Thanks for the support of the undergraduate research training programs of Capital Medical University(XSKY2023,XSKY2022,XSKY2021),China.We sincerely acknowledged that Professor Jianwei Jiao from the Institute of Zoology,Chinese Academy of Sciences,kindly provided the Nestin-Cre(C57BL/6.Cg-Tg(Nes-Cre)1Kln/J)mice.We sincerely appreciate for the technical service and support from Tissue Gnostics Asia Pacific Limited in the image caption and data analysis of immunohistochemical staining analysis.
文摘Choline acetyltransferase(ChAT)-positive neurons in neural stem cell(NSC)niches can evoke adult neurogenesis(AN)and restore impaired brain function after injury,such as acute ischemic stroke(AIS).However,the relevant mechanism by which ChAT+neurons develop in NSC niches is poorly understood.Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1(DDAH1),a hydrolase for asymmetric NG,NG-dimethylarginine(ADMA),regulated genes responsible for the synthesis and transportation of acetylcholine(ACh)(Chat,Slc5a7 and Slc18a3)after stroke insult.The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT,possibly through hypoxia-inducible factor 1α(HIF-1α).KC7F2,an inhibitor of HIF-1α,abolished DDAH1-induced ChAT expression and suppressed neurogenesis.As expected,DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity.By comparing the results among Ddah1 general knockout(KO)mice,transgenic(TG)mice and wild-type(WT)mice,we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone(SGZ)under ischemic insult.As a result,DDAH1 may promote cognitive and motor function recovery against stroke impairment,while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.
基金Publication of this paper is supported by the National Natural Science Foundation of China （30624808）.
文摘In the past decade, significant knowledge has accumulated regarding gibberellin （GA） signal transductlon In rice as a result of studies using multiple approaches, particularly molecular genetics. The present review highlights the recent developments In the identification of GA signaling pathway components, the discovery of GA-Induced destructlon of GA signaling repressor （DELLA protein）, and the possible mechanism underlying the regulation of GA- responsive gene expression in rice.
基金supported by the National Nature Science Foundation of China(81672607 and 81500077)the National Key Specialty Construction Project of Clinical Pharmacy(30305030698)+2 种基金the Nature Science Foundation of Beijing(7192143),the Beijing Nova Program(Z171100001117115)the Special Foundation for State Major Research Program of China(2016YFC0106603)the Research Funding of Sichuan Provincial People’s Hospital(2017LY08).
文摘Although targeted therapy has been extensively investigated for breast cancers,a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers.Mammaglobin-A(Mam-A),which is overexpressed in most breast carcinomas,has been proposed as a promising target.However,the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study.Here,seven potential epitopes of Mam-A were disclosed,and a unique epitope was then identified in most types of breast cancers,despite the genotypic heterogeneity.With phage display technology,the epitope was determined to be N-terminal amino acids 42–51 of Mam-A(N42–51).Then,the N42–51 epitope-specific monoclonal antibody,mAb785,was conjugated to poly lactic-co-glycolic acid(PLGA)nanoparticles loaded with therapeutic agents,thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers.The computer simulation of the N42–51 epitope and the mAb785 structures,as well as their interactions,further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.
