DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expressi...DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).展开更多
Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn...Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn's disease3,oesophagitis4 and multiple sclerosis5,6,and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence,in part by forming persistent pathogenic memory.Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7.Chronic rhinosinusitis affects more than 10%of the general population8.Among these patients,20-25%would develop nasal polyps,which often require repeated surgical resections owing to a high incidence of recurrence9.Whereas abundant T cells infiltrate the nasal polyps tissue10,11,T cell subsets that drive the disease pathology and promote recurrence are not fully understood.By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries,here we report that persistent CD8^(+)T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence,and these cells characteristically express the tryptase Granzyme K(GZMK).We find that GZMK cleaves many complement components,including C2,C3,C4 and C5,that collectively contribute to the activation of the complement cascade.GZMK-expressing CD8^(+)T cells participate in organized tertiary lymphoid structures,and tissue GZMK levels predict the disease severity and comorbidities better than well-established biomarkers such as eosinophilia and tissue interleukin-5.Using a mouse asthma model,we further show that GZMK-expressing CD8^(+)T cells exacerbate the disease in a manner dependent on the proteolytic activity of GZMK and complements.Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviates tissue pathology and restores lung function.Our work identifies a pathogenic CD8^(+)memory T cell subset that promotes tissue inflammation and recurrent airway diseases by the effector molecule GZMK and suggests GZMK as a potential therapeutic target.展开更多
Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health chall...Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health challenges due to TBI,particularly in military settings,where combat-related injuries introduce unique considerations for prevalence and management[2].Despite notable advancements in acute care,our comprehension of the complex pathophysiological mechanisms underlying the long-term eff ects of TBI remains inadequate[3].Although the initial mechanical impact triggers the cascade of injury,it is often the subsequent neuroinfl ammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments[4,5].展开更多
Cultures are different between western countries and China,and people's ways of expressing their love are also different.Thes edifferences badly influence well communication between lovers and family members.By co...Cultures are different between western countries and China,and people's ways of expressing their love are also different.Thes edifferences badly influence well communication between lovers and family members.By comparing the different ways of expressing love between western people and Chinese,this paper tries to make readers deeply recognize and make use of the differences of expressing love.展开更多
BACKGROUND For patients with coronary heart disease,reperfusion treatment strategies are often complicated by ischemia/reperfusion(I/R)injury(IRI),leading to serious organ damage and malfunction.The miR-21/programmed ...BACKGROUND For patients with coronary heart disease,reperfusion treatment strategies are often complicated by ischemia/reperfusion(I/R)injury(IRI),leading to serious organ damage and malfunction.The miR-21/programmed cell death protein 4(PDCD4)pathway is involved in the IRI of cardiomyocytes;however,the aberrant miR-21 expression remains unexplained.Therefore,this study aimed to explore whether circRNA_0031672 downregulates miR-21-5p expression during I/R and to dete-rmine whether miR-21-5p-expressing bone marrow mesenchymal stem cells(BMSCs)reduce myocardial IRI.METHODS CircRNA_0031672,miR-21-5p,and PDCD4 expressions were evaluated in the I/R rat model and hypoxia/re-oxy-genation(H/R)-treated H9C2 cells.Their interactions were subsequently investigated using luciferase reporter and RNA pull-down assays.Methyltransferase-like 3,a methyltransferase catalyzing N6-methyladenosine(m6A),was overexpressed in H9C2 cells to determine whether m6A modification influences miR-21-5p targeting PDCD4.BMSCs stably expressing miR-21 were co-cultured with H9C2 cells to investigate the protective effect of BMSCs on H9C2 cells upon H/R.RESULTS I/R downregulated miR-21-5p expression and upregulated circRNA_0031672 and PDCD4 expressions.CircRNA_0031672 knockdown increased miR-21-5p expression,but repressed PDCD4 expression,indicating that circRNA_0031672 com-petitively bound to miR-21-5p and prevented it from targeting PDCD4 mRNA.The m6A modification regulated PDCD4 expres-sion,but had no effect on miR-21-5p targeting PDCD4.The circRNA_0031672/miR-21-5p/PDCD4 axis regulated myocardial cells viability and apoptosis after H/R treatment;co-culture with miR-21-5p-expressing BMSCs restored miR-21-5p abundance in H9C2 cells and further reduced H9C2 cells apoptosis induced by H/R.CONCLUSIONS We identified a novel circRNA_0031672/miR-21-5p/PDCD4 signaling pathway that mediates the apoptosis of cardiomyocytes and successfully alleviates IRI in myocardial cells by co-culture with miR-21-5p-expressing BMSCs,offering novel insights into the IRI pathogenesis in cardiovascular diseases.展开更多
The CBF signal pathway is responsible for a significant portion of plant responses to low temperature and freezing.Overexpression of CBF genes in model organisms such as Arabidopsis thaliana enhances abiotic stress to...The CBF signal pathway is responsible for a significant portion of plant responses to low temperature and freezing.Overexpression of CBF genes in model organisms such as Arabidopsis thaliana enhances abiotic stress tolerance but also reduces growth.In addition to these effects,overexpression of the peach(Prunus persica[L.]Batsch)CBF1 gene in transgenic apple(Malus x domestica Borkh.)line T166 also results in early entry into and late exit from dormancy.Although the regulation of dormancy-induction and dormancy-release occur while the CBF regulon is operative in perennial,woody plants,how overexpression of CBF1 affects these dormancy-related changes in gene expression is incompletely understood.The objective of the present study was to characterize global changes in gene expression in peach CBF1-overexpressing and non-transformed apple bark tissues at different states of dormancy via RNA-seq.RNAseq bioinformatics data was confirmed by RT-qPCR on a number of genes.Results indicate that the greatest number of significantly differentially expressed genes(DEGs)occurred in April when dormancy release and bud break normally occur but are delayed in Line T166.Genes involved in storage and inactivation of auxin,GA,and cytokinin were generally upregulated in T166 in April,while those for biosynthesis,uptake or signal transduction were generally downregulated in T166.Genes for cell division and cambial growth were also downregulated in T166 relative to the non-transformed line.These data suggest that overexpression of the peach CBF1 gene impacts growth hormone homeostasis and as a result the activation of growth in the spring,and most likely growth cessation in the fall as well.展开更多
African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the ...African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus(r NDV) expressing ASFV protein 72(p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, r NDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in r NDV/p72 was stably maintained through ten passages. Mice immunized with r NDV/p72 developed high titers of ASFV p72 specific Ig G antibody, and had higher levels of Ig G1 than IgG2 a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that r NDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.展开更多
Grapevine downy mildew(DM)is a destructive oomycete disease of viticulture worldwide.MrRPV1 is a typical TIR-NBS-LRR type DM disease resistance gene cloned from the wild North American grapevine species Muscadinia rot...Grapevine downy mildew(DM)is a destructive oomycete disease of viticulture worldwide.MrRPV1 is a typical TIR-NBS-LRR type DM disease resistance gene cloned from the wild North American grapevine species Muscadinia rotundifolia.However,the molecular basis of resistance mediated by MrRPV1 remains poorly understood.Downy mildew-susceptible Vitis vinifera cv.Shiraz was transformed with a genomic fragment containing MrRPV1 to produce DM-resistant transgenic Shiraz lines.Comparative transcriptome analysis was used to compare the transcriptome profiles of the resistant and susceptible genotypes after DM infection.Transcriptome modulation during the response to P.viticola infection was more rapid,and more genes were induced in MrRPV1-transgenic Shiraz than in wild-type plants.In DM-infected MrRPV1-transgenic plants,activation of genes associated with Ca^(2+)release and ROS production was the earliest transcriptional response.Functional analysis of differentially expressed genes revealed that key genes related to multiple phytohormone signaling pathways and secondary metabolism were highly induced during infection.Coexpression network and motif enrichment analysis showed that WRKY and MYB transcription factors strongly coexpress with stilbene synthase(VvSTS)genes during defense against P.viticola in MrRPV1-transgenic plants.Taken together,these findings indicate that multiple pathways play important roles in MrRPV1-mediated resistance to downy mildew.展开更多
Whitefly-transmitted begomoviruses are economically important plant pathogens that cause severe problems in many crop plants,such as tomato,papaya,cotton,and tobacco.Tomato yellow leaf curl virus(TYLCV)is a typical mo...Whitefly-transmitted begomoviruses are economically important plant pathogens that cause severe problems in many crop plants,such as tomato,papaya,cotton,and tobacco.Tomato yellow leaf curl virus(TYLCV)is a typical monopartite begomovirus that has been extensively studied,but methods that can efficiently control begomoviruses are still scarce.In this study,we combined artificial microRNA(amiRNA)-mediated silencing technology and clay nanosheetmediated delivery by spraying and developed a method for efficiently preventing TYLCV infection in tomato plants.We designed three amiRNAs that target different regions of TYLCV to silence virus-produced transcripts.Three plant expression vectors expressing pre-amiRNAs were constructed,and recombinant plasmid DNAs(pDNAs)were loaded onto nontoxic and degradable layered double hydroxide(LDH)clay nanosheets.LDH nanosheets containing multiple pDNAs were sprayed onto plant leaves.We found that the designed amiRNAs were significantly accumulated in leaves 7 days after spraying,while the pDNAs were sustainably detected for 35 days after the spray,suggesting that the LDH nanosheets released pDNAs in a sustained manner,protected pDNAs from degradation and efficiently delivered pDNAs into plant cells.Importantly,when the LDH nanosheets coated with pDNAs were sprayed onto plants infected by TYLCV,both the disease severity and TYLCV viral concentration in sprayed plants were significantly decreased during the 35 days,while the levels of H_(2)O_(2) were significantly increased in those plants.Taken together,these results indicate that LDH nanosheets loaded with pDNAs expressing amiRNAs can be a sustainable and promising tool for begomovirus control.展开更多
Chilling stress is a production constraint of tomato,a tropical origin,chilling-sensitive horticultural crop.The development of chilling tolerant tomato thus has significant potential to impact tomato production.Gluta...Chilling stress is a production constraint of tomato,a tropical origin,chilling-sensitive horticultural crop.The development of chilling tolerant tomato thus has significant potential to impact tomato production.Glutaredoxins(GRXs)are ubiquitous oxidoreductases,which utilize the reducing power of glutathione to reduce disulfide bonds of substrate proteins and maintain cellular redox homeostasis.Here,we report that tomato expressing Arabidopsis GRX gene AtGRXS17 conferred tolerance to chilling stress without adverse effects on growth and development.AtGRXS17-expressing tomato plants displayed lower ion leakage,higher maximal photochemical efficiency of photosystem II(Fv/Fm)and increased accumulation of soluble sugar compared with wild-type plants after the chilling stress challenge.Furthermore,chilling tolerance was correlated with increased antioxidant enzyme activities and reduced H2O2 accumulation.At the same time,temporal expression patterns of the endogenous C-repeat/DRE-binding factor 1(SlCBF1)and CBF mediated-cold regulated genes were not altered in AtGRXS17-expressing plants when compared with wild-type plants,and proline concentrations remained unchanged relative to wild-type plants under chilling stress.Green fluorescent protein-AtGRXS17 fusion proteins,which were initially localized in the cytoplasm,migrated into the nucleus during chilling stress,reflecting a possible role of AtGRXS17 in nuclear signaling of chilling stress responses.Together,our findings demonstrate that genetically engineered tomato plants expressing AtGRXS17 can enhance chilling tolerance and suggest a genetic engineering strategy to improve chilling tolerance without yield penalty across different crop species.展开更多
Heat shock protein 90 (Hsp90) is a major heatshock protein whose functions are necessary for livingorganisms, including both procaryotes and eucaryotes.Human Hsp90 consists of two forms, Hsp90α andHsp90β. Expression...Heat shock protein 90 (Hsp90) is a major heatshock protein whose functions are necessary for livingorganisms, including both procaryotes and eucaryotes.Human Hsp90 consists of two forms, Hsp90α andHsp90β. Expression of Hsp90α appears to be inducible bydifferent stimuli. Adenovirus EIA gene products andtransformation with the H-ras oncogene can induce aselective overexpression of Hsp90α. Hsp90α was展开更多
Cotton,the most important natural fiber crop in the world,is a mainstay in China's economy.However,for over two decades,cotton yields both in China and U.S.have been at a plateau.
Dear Editor,Infectious bursal disease virus（IBDV）causes infectious bursal disease,a highly contagious immunosuppressive disease that affects young chickens and causes economic losses in the poultry industry worldwid...Dear Editor,Infectious bursal disease virus（IBDV）causes infectious bursal disease,a highly contagious immunosuppressive disease that affects young chickens and causes economic losses in the poultry industry worldwide.IBDV replicates mainly in actively dividing B lymphocytes within the bursa of Fabricius（BF）,leading to immunosuppression in affected flocks（Mahgoub et al.,2012）.Viral protein 2（VP2）,展开更多
Light is an electromagnetic stimulus that in mammals is sensed by specialized neurons in the retina.The physiological response to light encompasses two fundamental and different functional outputs：image-forming and n...Light is an electromagnetic stimulus that in mammals is sensed by specialized neurons in the retina.The physiological response to light encompasses two fundamental and different functional outputs：image-forming and non-image forming.展开更多
[Objective] The aim was to establish the BHK-21 stable cell lines expressing T7 RNAP and GFP.[Method]T7 RNAP gene was amplified from E.coli BL21（DE3）and inserted into FG12 vector.The lenti-virus recombinant plasmid ...[Objective] The aim was to establish the BHK-21 stable cell lines expressing T7 RNAP and GFP.[Method]T7 RNAP gene was amplified from E.coli BL21（DE3）and inserted into FG12 vector.The lenti-virus recombinant plasmid FG12-T7 RNAP plasmid was obtained via identification with double enzymes digestion and gene sequencing.The transient expressed T7 RNAP protein was determined by WB in 293T cells transfected with FG12-T7 RNAP plasmid.The recombinant FG12-RNAP lenti-virus was packaged up by transfecting the 293 cells with the recombinant vector FG12-RNAP and the helper plasmids via lipofectamine-2000,which was then used to infect BHK-21 cells.The positive cell clones were obtained after continuous screening by GFP.The expression of T7 RNAP gene was confirmed by Western blot.[Result]The cell line stably expressing the T7 RNAP gene was established by Western blot.[Conclusion]T7 RNAP gene could be stably expressed in eukaryotic cells and it provided a good platform to rescue RNA virus in vivo.展开更多
Local culture resources were excavated and expressed in environmental landscape section of ‘Miaojiang ·Yujinyuan’ residential plot in Taijiang County of Guizhou Province, with lusheng, Bronze drum and national ...Local culture resources were excavated and expressed in environmental landscape section of ‘Miaojiang ·Yujinyuan’ residential plot in Taijiang County of Guizhou Province, with lusheng, Bronze drum and national architecture as design elements. Making environmental landscape of residential plot, where the minority nationality lived in, possess culture agreement and emotion arrangement.展开更多
Patients with malignant glioma have a poorprognosis despite the combined use of surgery,irradiation, chemotherapy, and a variety ofimmunotherapies. These patient are known to showdecreased circulatory immune function ...Patients with malignant glioma have a poorprognosis despite the combined use of surgery,irradiation, chemotherapy, and a variety ofimmunotherapies. These patient are known to showdecreased circulatory immune function and suppression ofthe tumor-specific immune response. Interferon-γ(IFN-展开更多
Interleukin-12, a heterodimer produced mainlyby antigen presenting cells (APCs), plays vital rolesin the induction of Thl-mediated immune responsesand has the potential to treat cancer and infectiousdiseases. Systemic...Interleukin-12, a heterodimer produced mainlyby antigen presenting cells (APCs), plays vital rolesin the induction of Thl-mediated immune responsesand has the potential to treat cancer and infectiousdiseases. Systemic administration of IL-12 wasobserved to be associated with severe toxicity. To takefull advantage of its immunoregulatory activities andminimize its toxicities, local administration of IL-12may be the ideal approach. Intratumoral injection展开更多
In recent years, great enthusiasm is given to theresearches of cancer gene therapy, which seems to bea promising novel strategy for cancer treatment.There are several strategies to deliver target genes intobodies. Amo...In recent years, great enthusiasm is given to theresearches of cancer gene therapy, which seems to bea promising novel strategy for cancer treatment.There are several strategies to deliver target genes intobodies. Among them, adenovirus-mediated genetransfection exhibits great advantages including highgene transfer efficiency and high expression level. Butthe optimal route of gene delivery is still uncertain.展开更多
Apolipoprotein CⅢ(ApoCⅢ)has been implicated in hypertriglyceridemia and plasma ApoCⅢ is independently predicted as risk factor for coronary heart disease.Hypertriglyceridemia in patients are demonstrated to correla...Apolipoprotein CⅢ(ApoCⅢ)has been implicated in hypertriglyceridemia and plasma ApoCⅢ is independently predicted as risk factor for coronary heart disease.Hypertriglyceridemia in patients are demonstrated to correlate with elevated plasma ApoCⅢ levels and reduced lipoprotein lipase(LPL)activity,while展开更多
文摘DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).
文摘Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn's disease3,oesophagitis4 and multiple sclerosis5,6,and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence,in part by forming persistent pathogenic memory.Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7.Chronic rhinosinusitis affects more than 10%of the general population8.Among these patients,20-25%would develop nasal polyps,which often require repeated surgical resections owing to a high incidence of recurrence9.Whereas abundant T cells infiltrate the nasal polyps tissue10,11,T cell subsets that drive the disease pathology and promote recurrence are not fully understood.By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries,here we report that persistent CD8^(+)T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence,and these cells characteristically express the tryptase Granzyme K(GZMK).We find that GZMK cleaves many complement components,including C2,C3,C4 and C5,that collectively contribute to the activation of the complement cascade.GZMK-expressing CD8^(+)T cells participate in organized tertiary lymphoid structures,and tissue GZMK levels predict the disease severity and comorbidities better than well-established biomarkers such as eosinophilia and tissue interleukin-5.Using a mouse asthma model,we further show that GZMK-expressing CD8^(+)T cells exacerbate the disease in a manner dependent on the proteolytic activity of GZMK and complements.Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviates tissue pathology and restores lung function.Our work identifies a pathogenic CD8^(+)memory T cell subset that promotes tissue inflammation and recurrent airway diseases by the effector molecule GZMK and suggests GZMK as a potential therapeutic target.
基金supported by the National Natural Science Foundation of China(82102645)the Guangdong Basic and Applied Basic Research Foundation(2021A1515011042)the China Postdoctoral Science Foundation(2019M662995).
文摘Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health challenges due to TBI,particularly in military settings,where combat-related injuries introduce unique considerations for prevalence and management[2].Despite notable advancements in acute care,our comprehension of the complex pathophysiological mechanisms underlying the long-term eff ects of TBI remains inadequate[3].Although the initial mechanical impact triggers the cascade of injury,it is often the subsequent neuroinfl ammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments[4,5].
文摘Cultures are different between western countries and China,and people's ways of expressing their love are also different.Thes edifferences badly influence well communication between lovers and family members.By comparing the different ways of expressing love between western people and Chinese,this paper tries to make readers deeply recognize and make use of the differences of expressing love.
基金supported by the Guangxi Natural Science Foundation(No.2018GXNSFAA294137&No.2020GXNSFDA238007).
文摘BACKGROUND For patients with coronary heart disease,reperfusion treatment strategies are often complicated by ischemia/reperfusion(I/R)injury(IRI),leading to serious organ damage and malfunction.The miR-21/programmed cell death protein 4(PDCD4)pathway is involved in the IRI of cardiomyocytes;however,the aberrant miR-21 expression remains unexplained.Therefore,this study aimed to explore whether circRNA_0031672 downregulates miR-21-5p expression during I/R and to dete-rmine whether miR-21-5p-expressing bone marrow mesenchymal stem cells(BMSCs)reduce myocardial IRI.METHODS CircRNA_0031672,miR-21-5p,and PDCD4 expressions were evaluated in the I/R rat model and hypoxia/re-oxy-genation(H/R)-treated H9C2 cells.Their interactions were subsequently investigated using luciferase reporter and RNA pull-down assays.Methyltransferase-like 3,a methyltransferase catalyzing N6-methyladenosine(m6A),was overexpressed in H9C2 cells to determine whether m6A modification influences miR-21-5p targeting PDCD4.BMSCs stably expressing miR-21 were co-cultured with H9C2 cells to investigate the protective effect of BMSCs on H9C2 cells upon H/R.RESULTS I/R downregulated miR-21-5p expression and upregulated circRNA_0031672 and PDCD4 expressions.CircRNA_0031672 knockdown increased miR-21-5p expression,but repressed PDCD4 expression,indicating that circRNA_0031672 com-petitively bound to miR-21-5p and prevented it from targeting PDCD4 mRNA.The m6A modification regulated PDCD4 expres-sion,but had no effect on miR-21-5p targeting PDCD4.The circRNA_0031672/miR-21-5p/PDCD4 axis regulated myocardial cells viability and apoptosis after H/R treatment;co-culture with miR-21-5p-expressing BMSCs restored miR-21-5p abundance in H9C2 cells and further reduced H9C2 cells apoptosis induced by H/R.CONCLUSIONS We identified a novel circRNA_0031672/miR-21-5p/PDCD4 signaling pathway that mediates the apoptosis of cardiomyocytes and successfully alleviates IRI in myocardial cells by co-culture with miR-21-5p-expressing BMSCs,offering novel insights into the IRI pathogenesis in cardiovascular diseases.
文摘The CBF signal pathway is responsible for a significant portion of plant responses to low temperature and freezing.Overexpression of CBF genes in model organisms such as Arabidopsis thaliana enhances abiotic stress tolerance but also reduces growth.In addition to these effects,overexpression of the peach(Prunus persica[L.]Batsch)CBF1 gene in transgenic apple(Malus x domestica Borkh.)line T166 also results in early entry into and late exit from dormancy.Although the regulation of dormancy-induction and dormancy-release occur while the CBF regulon is operative in perennial,woody plants,how overexpression of CBF1 affects these dormancy-related changes in gene expression is incompletely understood.The objective of the present study was to characterize global changes in gene expression in peach CBF1-overexpressing and non-transformed apple bark tissues at different states of dormancy via RNA-seq.RNAseq bioinformatics data was confirmed by RT-qPCR on a number of genes.Results indicate that the greatest number of significantly differentially expressed genes(DEGs)occurred in April when dormancy release and bud break normally occur but are delayed in Line T166.Genes involved in storage and inactivation of auxin,GA,and cytokinin were generally upregulated in T166 in April,while those for biosynthesis,uptake or signal transduction were generally downregulated in T166.Genes for cell division and cambial growth were also downregulated in T166 relative to the non-transformed line.These data suggest that overexpression of the peach CBF1 gene impacts growth hormone homeostasis and as a result the activation of growth in the spring,and most likely growth cessation in the fall as well.
基金financially supported by the National Supporting Program(2013BAD12B05)Natural Science Foundation of China(NSFC)(no.31101839 and no.31302117)+1 种基金the key program of Gansu Province(no.1013JHTA008)Jiangsu Co-innovation Center program for Prevention and Control of Important Animal Infectious Diseases and Zoonoses
文摘African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus(r NDV) expressing ASFV protein 72(p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, r NDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in r NDV/p72 was stably maintained through ten passages. Mice immunized with r NDV/p72 developed high titers of ASFV p72 specific Ig G antibody, and had higher levels of Ig G1 than IgG2 a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that r NDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.
基金This research was supported by the National Natural Science Foundation of China(Grant nos.31660567 and 31760505),the Bagui Young Scholars’special fund of Guangxi,the Young Elite Scientists Sponsorship Program by CAST(Project No.2017QNRC001),and the Science and Technology Development Fund of Guangxi(2018GXNSFDA281019,GuikeAD18281056).We also thank Nayana Arunasiri for preparing the P.viticola inoculum and assisting with the time course infection experiment and Angelica Jermakow for preparing the total RNA samples.
文摘Grapevine downy mildew(DM)is a destructive oomycete disease of viticulture worldwide.MrRPV1 is a typical TIR-NBS-LRR type DM disease resistance gene cloned from the wild North American grapevine species Muscadinia rotundifolia.However,the molecular basis of resistance mediated by MrRPV1 remains poorly understood.Downy mildew-susceptible Vitis vinifera cv.Shiraz was transformed with a genomic fragment containing MrRPV1 to produce DM-resistant transgenic Shiraz lines.Comparative transcriptome analysis was used to compare the transcriptome profiles of the resistant and susceptible genotypes after DM infection.Transcriptome modulation during the response to P.viticola infection was more rapid,and more genes were induced in MrRPV1-transgenic Shiraz than in wild-type plants.In DM-infected MrRPV1-transgenic plants,activation of genes associated with Ca^(2+)release and ROS production was the earliest transcriptional response.Functional analysis of differentially expressed genes revealed that key genes related to multiple phytohormone signaling pathways and secondary metabolism were highly induced during infection.Coexpression network and motif enrichment analysis showed that WRKY and MYB transcription factors strongly coexpress with stilbene synthase(VvSTS)genes during defense against P.viticola in MrRPV1-transgenic plants.Taken together,these findings indicate that multiple pathways play important roles in MrRPV1-mediated resistance to downy mildew.
基金funded by the National Natural Science Foundation of China(31801707)the Key Projects of Science and Technology Research in Henan Province(182102110470)+3 种基金the Plant Protection of Key Discipline Project of Henan province(107020219001/005)the National Key Research and Development Program of China(2016YFD0300203-3)First-Class Postdoctoral Research Grant in Henan Province(001701038)the Science-Technology Foundation for High Level Talent of Henan Institute of Science and Technology(2015028).
文摘Whitefly-transmitted begomoviruses are economically important plant pathogens that cause severe problems in many crop plants,such as tomato,papaya,cotton,and tobacco.Tomato yellow leaf curl virus(TYLCV)is a typical monopartite begomovirus that has been extensively studied,but methods that can efficiently control begomoviruses are still scarce.In this study,we combined artificial microRNA(amiRNA)-mediated silencing technology and clay nanosheetmediated delivery by spraying and developed a method for efficiently preventing TYLCV infection in tomato plants.We designed three amiRNAs that target different regions of TYLCV to silence virus-produced transcripts.Three plant expression vectors expressing pre-amiRNAs were constructed,and recombinant plasmid DNAs(pDNAs)were loaded onto nontoxic and degradable layered double hydroxide(LDH)clay nanosheets.LDH nanosheets containing multiple pDNAs were sprayed onto plant leaves.We found that the designed amiRNAs were significantly accumulated in leaves 7 days after spraying,while the pDNAs were sustainably detected for 35 days after the spray,suggesting that the LDH nanosheets released pDNAs in a sustained manner,protected pDNAs from degradation and efficiently delivered pDNAs into plant cells.Importantly,when the LDH nanosheets coated with pDNAs were sprayed onto plants infected by TYLCV,both the disease severity and TYLCV viral concentration in sprayed plants were significantly decreased during the 35 days,while the levels of H_(2)O_(2) were significantly increased in those plants.Taken together,these results indicate that LDH nanosheets loaded with pDNAs expressing amiRNAs can be a sustainable and promising tool for begomovirus control.
基金We thank Dr.Barbara Valent for supplying pBV579(35S::mCherry::NLS::Tnos)This research was supported by the Kansas State University AES project NAHF381121(to S.H.P.,Q.W.,S.A.S.)National Science Foundation award IOS-1258028(F.F.W.,Y.H.,J.P.).
文摘Chilling stress is a production constraint of tomato,a tropical origin,chilling-sensitive horticultural crop.The development of chilling tolerant tomato thus has significant potential to impact tomato production.Glutaredoxins(GRXs)are ubiquitous oxidoreductases,which utilize the reducing power of glutathione to reduce disulfide bonds of substrate proteins and maintain cellular redox homeostasis.Here,we report that tomato expressing Arabidopsis GRX gene AtGRXS17 conferred tolerance to chilling stress without adverse effects on growth and development.AtGRXS17-expressing tomato plants displayed lower ion leakage,higher maximal photochemical efficiency of photosystem II(Fv/Fm)and increased accumulation of soluble sugar compared with wild-type plants after the chilling stress challenge.Furthermore,chilling tolerance was correlated with increased antioxidant enzyme activities and reduced H2O2 accumulation.At the same time,temporal expression patterns of the endogenous C-repeat/DRE-binding factor 1(SlCBF1)and CBF mediated-cold regulated genes were not altered in AtGRXS17-expressing plants when compared with wild-type plants,and proline concentrations remained unchanged relative to wild-type plants under chilling stress.Green fluorescent protein-AtGRXS17 fusion proteins,which were initially localized in the cytoplasm,migrated into the nucleus during chilling stress,reflecting a possible role of AtGRXS17 in nuclear signaling of chilling stress responses.Together,our findings demonstrate that genetically engineered tomato plants expressing AtGRXS17 can enhance chilling tolerance and suggest a genetic engineering strategy to improve chilling tolerance without yield penalty across different crop species.
文摘Heat shock protein 90 (Hsp90) is a major heatshock protein whose functions are necessary for livingorganisms, including both procaryotes and eucaryotes.Human Hsp90 consists of two forms, Hsp90α andHsp90β. Expression of Hsp90α appears to be inducible bydifferent stimuli. Adenovirus EIA gene products andtransformation with the H-ras oncogene can induce aselective overexpression of Hsp90α. Hsp90α was
基金This work is supported by the Major State Basic Research Development Program of China(2004CB117300)the National Natural Science Foundation of China (30530490)
文摘Cotton,the most important natural fiber crop in the world,is a mainstay in China's economy.However,for over two decades,cotton yields both in China and U.S.have been at a plateau.
基金supported by grants AERG 232141/PNBIO 1131032 from the Instituto Nacional de Tecnología Agropecuaria(INTA)PICT 2008-0400 from the Agencia Nacional de Promoción Científica y Tecnológica(ANPCyT),Argentina
文摘Dear Editor,Infectious bursal disease virus（IBDV）causes infectious bursal disease,a highly contagious immunosuppressive disease that affects young chickens and causes economic losses in the poultry industry worldwide.IBDV replicates mainly in actively dividing B lymphocytes within the bursa of Fabricius（BF）,leading to immunosuppression in affected flocks（Mahgoub et al.,2012）.Viral protein 2（VP2）,
基金supported by the Spanish Ministry of Education and Science SAF2015-67643-PSpanish Ministry of Economy and Competitiveness ISCIII-FEDER “Una manera de hacer Europa” PI13/00643
文摘Light is an electromagnetic stimulus that in mammals is sensed by specialized neurons in the retina.The physiological response to light encompasses two fundamental and different functional outputs：image-forming and non-image forming.
基金Supported by National Transgenic Major Program of China(2009ZX08007-006B)the National Natural Science Foundation of China(31072160)+2 种基金Science and Technique Foundation of Shandong Province(2009GG20002032)Natural Science Foundation of Shandong Province(Y2008D20)an Open Issue of State Key Laboratory of Veterinary Biotechnology Fund(SKLVBF200806)~~
文摘[Objective] The aim was to establish the BHK-21 stable cell lines expressing T7 RNAP and GFP.[Method]T7 RNAP gene was amplified from E.coli BL21（DE3）and inserted into FG12 vector.The lenti-virus recombinant plasmid FG12-T7 RNAP plasmid was obtained via identification with double enzymes digestion and gene sequencing.The transient expressed T7 RNAP protein was determined by WB in 293T cells transfected with FG12-T7 RNAP plasmid.The recombinant FG12-RNAP lenti-virus was packaged up by transfecting the 293 cells with the recombinant vector FG12-RNAP and the helper plasmids via lipofectamine-2000,which was then used to infect BHK-21 cells.The positive cell clones were obtained after continuous screening by GFP.The expression of T7 RNAP gene was confirmed by Western blot.[Result]The cell line stably expressing the T7 RNAP gene was established by Western blot.[Conclusion]T7 RNAP gene could be stably expressed in eukaryotic cells and it provided a good platform to rescue RNA virus in vivo.
文摘Local culture resources were excavated and expressed in environmental landscape section of ‘Miaojiang ·Yujinyuan’ residential plot in Taijiang County of Guizhou Province, with lusheng, Bronze drum and national architecture as design elements. Making environmental landscape of residential plot, where the minority nationality lived in, possess culture agreement and emotion arrangement.
文摘Patients with malignant glioma have a poorprognosis despite the combined use of surgery,irradiation, chemotherapy, and a variety ofimmunotherapies. These patient are known to showdecreased circulatory immune function and suppression ofthe tumor-specific immune response. Interferon-γ(IFN-
文摘Interleukin-12, a heterodimer produced mainlyby antigen presenting cells (APCs), plays vital rolesin the induction of Thl-mediated immune responsesand has the potential to treat cancer and infectiousdiseases. Systemic administration of IL-12 wasobserved to be associated with severe toxicity. To takefull advantage of its immunoregulatory activities andminimize its toxicities, local administration of IL-12may be the ideal approach. Intratumoral injection
文摘In recent years, great enthusiasm is given to theresearches of cancer gene therapy, which seems to bea promising novel strategy for cancer treatment.There are several strategies to deliver target genes intobodies. Among them, adenovirus-mediated genetransfection exhibits great advantages including highgene transfer efficiency and high expression level. Butthe optimal route of gene delivery is still uncertain.
文摘Apolipoprotein CⅢ(ApoCⅢ)has been implicated in hypertriglyceridemia and plasma ApoCⅢ is independently predicted as risk factor for coronary heart disease.Hypertriglyceridemia in patients are demonstrated to correlate with elevated plasma ApoCⅢ levels and reduced lipoprotein lipase(LPL)activity,while
