Objective To explore the clinical significance of the combined application of palpebral margin cleaning and antibiotic eye drops in inhibiting bacterial growth in the palpebral margin and conjunctival sacs before cata...Objective To explore the clinical significance of the combined application of palpebral margin cleaning and antibiotic eye drops in inhibiting bacterial growth in the palpebral margin and conjunctival sacs before cataract extraction.Methods In this study,61 patients(97 eyes)with age-related cataract who underwent phacoemulsification and intraocular lens implantation were selected,and randomly grouped.In the experimental group,the combined application of palpebral margin cleaning with cotton pads and levofloxacin eye drops was given for three days before the surgery.In the control group,levofloxacin eye drops alone were applied for three consecutive days.Bacteria samples from the conjunctival sac and eyelid margins were cultivated and identified before and three days after taking antimicrobial measures,respectively.Results In the experimental group,the positive rates of the two bacteria samples were 100%(50/50)and 40%(20/50)before and 10%(5/50)and 0%(0/50)after the treatment.In the control group,the positive rates of the two bacteria samples were 97.9%(46/47)and 29.8%(14/47)before and 40.4%(19/47)and 10.6%(5/47)after the treatment.The positive rates between the two groups were not significantly different before taking antimicrobial measures(P=0.485 and 0.395),while they were significantly different after taking antimicrobial measures(P=0.001 and 0.024).Conclusion Combined application of eyelid and palpebral margin cleaning with cotton pads and antibiotic eye drops before cataract extraction imparted excellent antibacterial effects.展开更多
Wood-plastic composite is an environmentally friendly material,due to its use of recycled thermoplastics and plant fibers.However,its surface lacks attractive aesthetic qualities.In this paper,a method of decorating w...Wood-plastic composite is an environmentally friendly material,due to its use of recycled thermoplastics and plant fibers.However,its surface lacks attractive aesthetic qualities.In this paper,a method of decorating wood fiber/high-density polyethylene(WF/HDPE)without adding adhesive was explored.Canvas or polyester fabrics were selected as the surface decoration materials.The influence of hot-pressing temperature and WF/HDPE ratio on the adhesion was studied.The surface bonding strength,water resistance,and surface color were evaluated,and observation within the infrared spectrum and under scanning electron microscopy was used to analyze the bonding process.The results showed that the fabric and WF/HDPE substrate could be closely laminated together depending on the HDPE layer accumulated on the WF/HDPE surface.The molten HDPE matrix penetrates canvas more easily than polyester fabric,and the canvasveneered composite shows a greater bonding strength than does the polyester fabric-veneered composite.A higher proportion of the thermoplastic component in the substrate improved the bonding.When the hot-pressing temperature exceeded 160°C,the fabric-veneered WF/HDPE panels had greater water resistance,although the canvas fabric changed more obviously in terms of fiber shape and color,compared with the polyester fabric.For the canvas fabric,140°C–160°C was a suitable hot-pressing temperature,whereas 160°C–180°C was more suitable for polyester fabric.The proportion of the thermoplastic component in the composite should be not less than 30%to achieve adequate bonding strength.展开更多
Epithelial Protein Lost in Neoplasm (EPLIN) is a cytoskeletal associated protein implicated in regulating actin dynamoics and cellular motility and whose expression is frequently downregulated in a number of human can...Epithelial Protein Lost in Neoplasm (EPLIN) is a cytoskeletal associated protein implicated in regulating actin dynamoics and cellular motility and whose expression is frequently downregulated in a number of human cancers. The current study examined the expression levels of EPLIN-α in a pulmonary cancer cohort and its association with clinical pathological factors using quantitative polymerase chain reaction. Additionally, EPLIN-α was over-expressed in the SKMES-1 pulmonary cancer cell line through transfection with a plasmid containing the expression sequence for EPLIN-α. The role of EPLIN-α was subsequently examined using a variety of in vitro functional assays. Decreased levels of EPLIN-α were seen in cancerous tissues compared to normal background tissue. Lower levels of EPLIN-α were also associated with higher TNM stage and nodal involvement. In vitro over-expression of EPLIN-α inhibited SKMES-1 growth rates (p = 0.05 vs. plasmid control) and motility (p = 0.002 vs. plasmid control), though did not have any significant effects on cell-matrix adhesion or cell invasion. Taken together, the current study indicates that lower levels of EPLIN-α may be associated with poorer prognosis and more advanced pulmonary cancer, where this molecule appears to play a suppressive role on cell growth and migration.展开更多
The restriction of immunoglobulin(Ig)expression to B lymphocytes is well established.However,several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells.Our aim...The restriction of immunoglobulin(Ig)expression to B lymphocytes is well established.However,several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells.Our aim is to determine whether the Ig gene promoter can be activated in non-B cancer cells and to identify the regulatory mechanism for Ig gene expression.Our results show that the Ig promoter of VH4-59 was activated in several non-B cancer cell lines.Moreover,two novel positive regulatory elements,an enhancer-like element at 2800 to 2610 bp and a copromoter-like element at 2610 to 2300 bp,were identified in two epithelial cancer cell lines,HeLa S3 and HT-29.The octamer element(59-ATGCAAAT-39)located in the Ig promoter,a crucial element for B-cell-derived Ig gene transcription,was also very important for non-B-cell-derived Ig gene transcription.More importantly,we confirmed that octamer-related protein-1(Oct-1),but not Oct-2,was a crucial transcriptional factor for Ig gene transcription due to its ability to bind to the octamer element of the Ig promoter in epithelial cancer cells.These results suggested the presence of a distinct regulatory mechanism for Ig gene expression in non-B cancer cells.展开更多
HIV-1 infection-induced cGAS–STING–TBK1–IRF3 signaling activates innate immunity to produce type I interferon(IFN).The HIV-1 nonstructural protein viral infectivity factor(Vif)is essential in HIV-1 replication,as i...HIV-1 infection-induced cGAS–STING–TBK1–IRF3 signaling activates innate immunity to produce type I interferon(IFN).The HIV-1 nonstructural protein viral infectivity factor(Vif)is essential in HIV-1 replication,as it degrades the host restriction factor APOBEC3G.However,whether and how it regulates the host immune response remains to be determined.In this study,we found that Vif inhibited the production of type I IFN to promote immune evasion.HIV-1 infection induced the activation of the host tyrosine kinase FRK,which subsequently phosphorylated the immunoreceptor tyrosine-based inhibitory motif(ITIM)of Vif and enhanced the interaction between Vif and the cellular tyrosine phosphatase SHP-1 to inhibit type I IFN.Mechanistically,the association of Vif with SHP-1 facilitated SHP-1 recruitment to STING and inhibited the K63-linked ubiquitination of STING at Lys337 by dephosphorylating STING at Tyr162.However,the FRK inhibitor D-65495 counteracted the phosphorylation of Vif to block the immune evasion of HIV-1 and antagonize infection.These findings reveal a previously unknown mechanism through which HIV-1 evades antiviral immunity via the ITIM-containing protein to inhibit the posttranslational modification of STING.These results provide a molecular basis for the development of new therapeutic strategies to treat HIV-1 infection.展开更多
One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem(ES)cells,which is used to produce gene-targeted mice for wide applications in biomedicine.However,a major bott...One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem(ES)cells,which is used to produce gene-targeted mice for wide applications in biomedicine.However,a major bottleneck in this approach is that the robustness of germiine transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing,which impairs the efficiency and robustness of mouse model generation.Recently,we have established a new type of pluripotent cells termed extended pluripotent stem(EPS)cells,which have superior developmental potency and robust germline competence compared to conventional mouse ES cells.In this study,we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage.Based on gene targeting in mouse EPS cells,we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation,Haibo Li and Chaoran Zhao contributed equally to this work.Electronic supplementary material The online version of this article(https://doi.org/10.1007/s13238-018-0556-1)contains supplementary material,which is available to authorized users.which could be accomplished in approximately 2 months.Importantly,using this approach,we successfully constructed mouse models in which the human interleukin 3(IL3)or interleukin 6(IL6)gene was knocked into its corresponding locus in the mouse genome.Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting,which have great application potential in biomedical research.展开更多
Background:Methyltransferase 3(METTL3)-mediated N6-methyladenosine(m^(6)A)RNA modification has been demonstrated to be a potential factor in promoting gastric cancer(GC).METTL3 regulates a series of signaling pathways...Background:Methyltransferase 3(METTL3)-mediated N6-methyladenosine(m^(6)A)RNA modification has been demonstrated to be a potential factor in promoting gastric cancer(GC).METTL3 regulates a series of signaling pathways by modifying various mRNAs.This study aimed to identify novel METTL3-mediated signaling pathways and explored possible targets for use in the clinical setting of gastric cancer.Methods:To investigate the proliferation and metastatic capacity ofGCcell lines with METTL3 knockdown,a xenograft,lung metastasis,and popliteal lymph node metastasis model was used.Them^(6)A-modified RNA immunoprecipitation(Me-RIP)sequence was utilized to explore the target mRNAs of METTL3.Cell counting kit 8 and transwell assays were performed to investigate the promoting function of pre-B cell leukemia homeobox 1(PBX1)and GTP cyclohydrolase 1(GCH1).Western blotting and chromatin immunoprecipitation were employed to confirm the involvement of the METTL3-PBX1-GCH1 axis.ELISA and liquid chromatography-mass spectrometry were used to explore the biological function of tetrahydrobiopterin(BH_(4)).Results:Knockdown of METTL3 suppressed xenograft tumor growth and lung/lymph node metastasis in vivo.Mechanistically,we found that METTL3 combined with and stabilized PBX1 mRNAs.Chromatin immunoprecipitation(ChIP)and further experiments suggested that PBX1 acted as a transcription factor inducing GCH1 expression.Moreover,the METTL3-PBX1-GCH1 axis increased BH_(4)levels in GC cells,thereby promoting tumor progression.Conclusions:This study suggested that METTL3 enzymes promote tumor growth and lung/lymph node metastasis via METTL3-PBX1-GCH1 axis increasing BH_(4)levels in GC.展开更多
基金supported by the National Natural Science Foundation of China(81970768).
文摘Objective To explore the clinical significance of the combined application of palpebral margin cleaning and antibiotic eye drops in inhibiting bacterial growth in the palpebral margin and conjunctival sacs before cataract extraction.Methods In this study,61 patients(97 eyes)with age-related cataract who underwent phacoemulsification and intraocular lens implantation were selected,and randomly grouped.In the experimental group,the combined application of palpebral margin cleaning with cotton pads and levofloxacin eye drops was given for three days before the surgery.In the control group,levofloxacin eye drops alone were applied for three consecutive days.Bacteria samples from the conjunctival sac and eyelid margins were cultivated and identified before and three days after taking antimicrobial measures,respectively.Results In the experimental group,the positive rates of the two bacteria samples were 100%(50/50)and 40%(20/50)before and 10%(5/50)and 0%(0/50)after the treatment.In the control group,the positive rates of the two bacteria samples were 97.9%(46/47)and 29.8%(14/47)before and 40.4%(19/47)and 10.6%(5/47)after the treatment.The positive rates between the two groups were not significantly different before taking antimicrobial measures(P=0.485 and 0.395),while they were significantly different after taking antimicrobial measures(P=0.001 and 0.024).Conclusion Combined application of eyelid and palpebral margin cleaning with cotton pads and antibiotic eye drops before cataract extraction imparted excellent antibacterial effects.
基金supported by the National Natural Science Foundation of China[31670573]the Innovation Training Program of Northeast Forestry University[201810225398].
文摘Wood-plastic composite is an environmentally friendly material,due to its use of recycled thermoplastics and plant fibers.However,its surface lacks attractive aesthetic qualities.In this paper,a method of decorating wood fiber/high-density polyethylene(WF/HDPE)without adding adhesive was explored.Canvas or polyester fabrics were selected as the surface decoration materials.The influence of hot-pressing temperature and WF/HDPE ratio on the adhesion was studied.The surface bonding strength,water resistance,and surface color were evaluated,and observation within the infrared spectrum and under scanning electron microscopy was used to analyze the bonding process.The results showed that the fabric and WF/HDPE substrate could be closely laminated together depending on the HDPE layer accumulated on the WF/HDPE surface.The molten HDPE matrix penetrates canvas more easily than polyester fabric,and the canvasveneered composite shows a greater bonding strength than does the polyester fabric-veneered composite.A higher proportion of the thermoplastic component in the substrate improved the bonding.When the hot-pressing temperature exceeded 160°C,the fabric-veneered WF/HDPE panels had greater water resistance,although the canvas fabric changed more obviously in terms of fiber shape and color,compared with the polyester fabric.For the canvas fabric,140°C–160°C was a suitable hot-pressing temperature,whereas 160°C–180°C was more suitable for polyester fabric.The proportion of the thermoplastic component in the composite should be not less than 30%to achieve adequate bonding strength.
文摘Epithelial Protein Lost in Neoplasm (EPLIN) is a cytoskeletal associated protein implicated in regulating actin dynamoics and cellular motility and whose expression is frequently downregulated in a number of human cancers. The current study examined the expression levels of EPLIN-α in a pulmonary cancer cohort and its association with clinical pathological factors using quantitative polymerase chain reaction. Additionally, EPLIN-α was over-expressed in the SKMES-1 pulmonary cancer cell line through transfection with a plasmid containing the expression sequence for EPLIN-α. The role of EPLIN-α was subsequently examined using a variety of in vitro functional assays. Decreased levels of EPLIN-α were seen in cancerous tissues compared to normal background tissue. Lower levels of EPLIN-α were also associated with higher TNM stage and nodal involvement. In vitro over-expression of EPLIN-α inhibited SKMES-1 growth rates (p = 0.05 vs. plasmid control) and motility (p = 0.002 vs. plasmid control), though did not have any significant effects on cell-matrix adhesion or cell invasion. Taken together, the current study indicates that lower levels of EPLIN-α may be associated with poorer prognosis and more advanced pulmonary cancer, where this molecule appears to play a suppressive role on cell growth and migration.
基金supported by Fundamental Research Grants 30572094 and 30772470 from the Natural Sciences Foundation,China.We thank Dr Dalong Ma and Dr Mingxu Xu(Peking University Center for Human Disease Genomics)for their comments and suggestions.This manuscript was proofread by an English-speaking professional with a science background at Elixigen Corporation.
文摘The restriction of immunoglobulin(Ig)expression to B lymphocytes is well established.However,several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells.Our aim is to determine whether the Ig gene promoter can be activated in non-B cancer cells and to identify the regulatory mechanism for Ig gene expression.Our results show that the Ig promoter of VH4-59 was activated in several non-B cancer cell lines.Moreover,two novel positive regulatory elements,an enhancer-like element at 2800 to 2610 bp and a copromoter-like element at 2610 to 2300 bp,were identified in two epithelial cancer cell lines,HeLa S3 and HT-29.The octamer element(59-ATGCAAAT-39)located in the Ig promoter,a crucial element for B-cell-derived Ig gene transcription,was also very important for non-B-cell-derived Ig gene transcription.More importantly,we confirmed that octamer-related protein-1(Oct-1),but not Oct-2,was a crucial transcriptional factor for Ig gene transcription due to its ability to bind to the octamer element of the Ig promoter in epithelial cancer cells.These results suggested the presence of a distinct regulatory mechanism for Ig gene expression in non-B cancer cells.
基金This work was supported by grants from the Program of Shanghai Academic Research Leader(21XD1402900)the Natural Science Foundation of Shanghai(21ZR1481400)+3 种基金the National Natural Science Foundation of China(31972900)the National Youth Talent Support Program(Ten Thousand Talent Program)the National Key Research and Development Program of China(2018YFC1705505)the National Megaproject on Key Infectious Diseases(2017ZX10202102).
文摘HIV-1 infection-induced cGAS–STING–TBK1–IRF3 signaling activates innate immunity to produce type I interferon(IFN).The HIV-1 nonstructural protein viral infectivity factor(Vif)is essential in HIV-1 replication,as it degrades the host restriction factor APOBEC3G.However,whether and how it regulates the host immune response remains to be determined.In this study,we found that Vif inhibited the production of type I IFN to promote immune evasion.HIV-1 infection induced the activation of the host tyrosine kinase FRK,which subsequently phosphorylated the immunoreceptor tyrosine-based inhibitory motif(ITIM)of Vif and enhanced the interaction between Vif and the cellular tyrosine phosphatase SHP-1 to inhibit type I IFN.Mechanistically,the association of Vif with SHP-1 facilitated SHP-1 recruitment to STING and inhibited the K63-linked ubiquitination of STING at Lys337 by dephosphorylating STING at Tyr162.However,the FRK inhibitor D-65495 counteracted the phosphorylation of Vif to block the immune evasion of HIV-1 and antagonize infection.These findings reveal a previously unknown mechanism through which HIV-1 evades antiviral immunity via the ITIM-containing protein to inhibit the posttranslational modification of STING.These results provide a molecular basis for the development of new therapeutic strategies to treat HIV-1 infection.
基金the National Key Research and Development Program of China(2016YFA01001002017YFA0103000)+4 种基金the National Natural Science Foundation of China(Grant Nos.31730059 and 31521004)the Guangdong Innovative and En trepreneurial Research Team Program(2014ZT05S216)the Science and Technology Planning Project of Guangdong Province,China(2014B020226001 and 2016B030232001)the Science and Technology Program of Guangzhou,China(201508020001)National Natural Science Foundation of China(Grant No.31571052).
文摘One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem(ES)cells,which is used to produce gene-targeted mice for wide applications in biomedicine.However,a major bottleneck in this approach is that the robustness of germiine transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing,which impairs the efficiency and robustness of mouse model generation.Recently,we have established a new type of pluripotent cells termed extended pluripotent stem(EPS)cells,which have superior developmental potency and robust germline competence compared to conventional mouse ES cells.In this study,we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage.Based on gene targeting in mouse EPS cells,we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation,Haibo Li and Chaoran Zhao contributed equally to this work.Electronic supplementary material The online version of this article(https://doi.org/10.1007/s13238-018-0556-1)contains supplementary material,which is available to authorized users.which could be accomplished in approximately 2 months.Importantly,using this approach,we successfully constructed mouse models in which the human interleukin 3(IL3)or interleukin 6(IL6)gene was knocked into its corresponding locus in the mouse genome.Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting,which have great application potential in biomedical research.
基金Natural Science Foundation of Guangdong Province,Grant/Award Numbers:2018A030313634,2020A1515010214,2021A1515010473Guangdong Basic and Applied Basic Research Foundation,Grant/Award Numbers:2020A1515010214,2018A030313634,2021A1515010473+1 种基金Young Teacher Foundation of Sun Yat-sen University,Grant/Award Number:19ykpy58China Postdoctoral Science Foundation,Grant/Award Number:2020M683087。
文摘Background:Methyltransferase 3(METTL3)-mediated N6-methyladenosine(m^(6)A)RNA modification has been demonstrated to be a potential factor in promoting gastric cancer(GC).METTL3 regulates a series of signaling pathways by modifying various mRNAs.This study aimed to identify novel METTL3-mediated signaling pathways and explored possible targets for use in the clinical setting of gastric cancer.Methods:To investigate the proliferation and metastatic capacity ofGCcell lines with METTL3 knockdown,a xenograft,lung metastasis,and popliteal lymph node metastasis model was used.Them^(6)A-modified RNA immunoprecipitation(Me-RIP)sequence was utilized to explore the target mRNAs of METTL3.Cell counting kit 8 and transwell assays were performed to investigate the promoting function of pre-B cell leukemia homeobox 1(PBX1)and GTP cyclohydrolase 1(GCH1).Western blotting and chromatin immunoprecipitation were employed to confirm the involvement of the METTL3-PBX1-GCH1 axis.ELISA and liquid chromatography-mass spectrometry were used to explore the biological function of tetrahydrobiopterin(BH_(4)).Results:Knockdown of METTL3 suppressed xenograft tumor growth and lung/lymph node metastasis in vivo.Mechanistically,we found that METTL3 combined with and stabilized PBX1 mRNAs.Chromatin immunoprecipitation(ChIP)and further experiments suggested that PBX1 acted as a transcription factor inducing GCH1 expression.Moreover,the METTL3-PBX1-GCH1 axis increased BH_(4)levels in GC cells,thereby promoting tumor progression.Conclusions:This study suggested that METTL3 enzymes promote tumor growth and lung/lymph node metastasis via METTL3-PBX1-GCH1 axis increasing BH_(4)levels in GC.
