Viruses are representative of a global threat to agricultural production. Genetic resistance is the preferred strategy for the control of viral infection and against loss of crop yield. Viral protein synthesis require...Viruses are representative of a global threat to agricultural production. Genetic resistance is the preferred strategy for the control of viral infection and against loss of crop yield. Viral protein synthesis requires host cellular factors for translating their viral RNAs, and for regulating their replication and cell to cell systemic movement. Therefore, the viruses are dependent on cellular translation factors. Mutations in the gene encoding eIF4E and eIF4G or their isoforms, eIFiso4 E, eIFiso4 G and eIF2Bβ have been mapped as a source of plant potyvirus while other genus of plant virus recessive resistance genes in many species are originated from these loci. Some of other plant translation factors, such as eIF3,eIF4 A-like helicases, eEF1A and eEF1B, which are required in interacting with viral RNAs and regulating various aspects of the infection cycle,have also been identified. Here, we summarized the mechanisms utilized by RNA viruses of eukaryotic plants and the essential roles of e IFs in virus infection. Moreover, we discussed the potential of e IFs as a target gene in the development of genetic resistance to viruses for crop improvement. This review highlighted newly revealed examples of abnormal translational strategies and provided insights into natural host resistance mechanisms that have been linked to 3 cap-independent translational enhancer activity.展开更多
Fatigue failure continues to be a significant challenge in designing structural and mechanical components subjected to repeated and complex loading.While earlier studies mainly examined material properties and how str...Fatigue failure continues to be a significant challenge in designing structural and mechanical components subjected to repeated and complex loading.While earlier studies mainly examined material properties and how stress affects lifespan,this review offers the first comprehensive,multiscale comparison of strategies that optimize geometry to improve fatigue performance.This includes everything from microscopic features like the shape of graphite nodules to large-scale design elements such as fillets,notches,and overall structural layouts.We analyze and combine various methods,including topology and shape optimization,the ability of additive manufacturing to finetune internal geometries,and reliability-based design approaches.A key new contribution is our proposal of a standard way to evaluate geometry-focused fatigue design,allowing for consistent comparison and encouraging validation across different fields.Furthermore,we highlight important areas for future research,such as incorporating manufacturing flaws,using multiscale models,and integrating machine learning techniques.This work is the first to provide a broad geometric viewpoint in fatigue engineering,laying the groundwork for future design methods that are driven by data and centered on reliability.展开更多
The composition of magnesium alloys is greatly associated with initial deposition behavior of electroless Ni-P coatings.Thus,the initial deposition behavior of electroless Ni–P coatings on ZK60 and ME20 alloys was in...The composition of magnesium alloys is greatly associated with initial deposition behavior of electroless Ni-P coatings.Thus,the initial deposition behavior of electroless Ni–P coatings on ZK60 and ME20 alloys was investigated.The results indicated that differences in the alloy compositions significantly influenced the initial deposition process and the adhesive strength,corrosion resistance,and crystal structure.The initial deposition of coatings on ZK60 and ME20 alloys preferentially occurred on the precipitates.The precipitates in ZK60 alloy had higher chemical activity after HF activation and controlled the initial deposition rate of the coating.The initial deposition rate of the coating on ME20 alloy mainly depended on the density of the Mg F2 film formed by HF activation rather than on the precipitates.Owing to differences in the initial deposition process,the coating on ZK60 alloy had higher adhesive strength and better corrosion resistance than that on ME20 alloy.The coatings on ZK60 and ME20 alloys mainly had crystalline structures,and the coating on ME20 alloy had also a slight microcrystalline structure.展开更多
BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP...BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.展开更多
Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladde...Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.展开更多
Revised national tuberculosis control programme in India has limited co-hort-wise information about what happens to patients diagnosed with multidrug resistant TB (MDR-TB). We determined the pre-treatment loss to foll...Revised national tuberculosis control programme in India has limited co-hort-wise information about what happens to patients diagnosed with multidrug resistant TB (MDR-TB). We determined the pre-treatment loss to follow-up (non-initiation of treatment by programme within 6 months of diagnosis) and time from diagnosis to treatment initiation in Bhopal district, central India (2014). Pre-treatment loss to follow-up was 13% (0.95 CI: 7%, 23%), not significantly different from the national estimates (18%) and median time to initiate treatment was seven days, lower than that reported elsewhere in the country. Bhopal was performing well with reference to time to treatment initiation in programmatic settings.展开更多
Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise o...Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise of resistance-breaking(RB)strains and emerging potyviral species necessitates the development of more durable and broad-spectrum resistance strategies.In this study,our field survey in Yunnan,China,identified potato virus Y(PVY)RB isolates,as well as the prevalence of tobacco vein banding mosaic virus(TVBMV)and chilli veinal mottle virus(ChiVMV),in tobacco carrying the recessive va locus,which lacks the eIF4E1-S susceptibility gene,due to a chromosomal deletion.Protein interaction and viral infection assays demonstrated that both eIF4E1-S and eIFiso4E-T are used by PVY RB as susceptibility factors for infection,with the combined inactivation of these genes confering durable resistance.Similarly,the knockout of eIFiso4E-S,in the va genetic background,provided effective resistance to TVBMV and reduced susceptibility to ChiVMV.Notably,pyramiding mutations in eIFiso4E-S and eIFiso4E-T,in va tobacco,generated plants exhibiting robust,broad-spectrum resistance,to all three viruses,without compromising plant development.These findings underscore the potential of stacking eIF4E mutations to engineer durable,broad-spectrum resistance to potyviruses in tobacco,offering a promising strategy for crop improvement.展开更多
Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene a...Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers.Accumulated evidence shows that eIF5A2 initiates tumor formation,enhances cancer cell growth,increases cancer cell metastasis,and promotes treatment resistance through multiple means,including inducing epithelial–mesenchymal transition,cytoskeletal rearrangement,angiogenesis,and metabolic reprogramming.Expression of eIF5A2 in cancer correlates with poor survival,advanced disease stage,as well as metastasis,suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis.All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target.This review focuses on the expression,subcellular localization,post-translational modifications,and regulatory networks of eIF5A2,as well as its biochemical functions and evolving clinical applications in cancer,especially in human digestive system neoplasms.展开更多
In beam-to-column joint with bolted end-plate connection,the structural details of column flange reinforced by backing plate and column web panel reinforced by supplementary plate are analyzed.The joint is divided int...In beam-to-column joint with bolted end-plate connection,the structural details of column flange reinforced by backing plate and column web panel reinforced by supplementary plate are analyzed.The joint is divided into some basic components,and the initial stiffness of each component is obtained.Especially,the initial stiffness of reinforced components is drawn by theoretical model and finite element analysis.The initial stiffness of reinforced joint can be obtained by assembling the initial stiffness of each component.The design moment resistance of column flange reinforced by backing plate is deduced based on yield line method,and the design moment resistances of other components are deduced based on present codes.The design moment resistance of the reinforced joint is then determined by the minimum of the design moment resistances of all components.By comparison with the results of finite element calculation,it is verified that the method to calculate the initial stiffness of reinforced joint is accurate enough to be used to estimate the rigid behavior of the joint and to make parametric study.展开更多
To analyze the impact of bubbles on the mechanical behavior of glasses,by controlling the refining time,we prepared three borosilicate glasses with the same composition and different porosity.By the analysis software ...To analyze the impact of bubbles on the mechanical behavior of glasses,by controlling the refining time,we prepared three borosilicate glasses with the same composition and different porosity.By the analysis software integrated within the optical microscope,the diameter and number of the bubbles on the surface of three borosilicate glasses were quantified.From the hardness and crack initiation resistance(CR),we built the relationship between the porosity and the mechanical performance of these borosilicate glasses.展开更多
基金The authors thank Mr.Tomas Maher from the Department of Biology at the Pennsylvania State University for language editing.This work is supported by the National Natural Science Foundation of Zhejiang Province(Grant No.LZ20C150002)and the National Natural Science Foundation of China(Grant No.31872095).
文摘Viruses are representative of a global threat to agricultural production. Genetic resistance is the preferred strategy for the control of viral infection and against loss of crop yield. Viral protein synthesis requires host cellular factors for translating their viral RNAs, and for regulating their replication and cell to cell systemic movement. Therefore, the viruses are dependent on cellular translation factors. Mutations in the gene encoding eIF4E and eIF4G or their isoforms, eIFiso4 E, eIFiso4 G and eIF2Bβ have been mapped as a source of plant potyvirus while other genus of plant virus recessive resistance genes in many species are originated from these loci. Some of other plant translation factors, such as eIF3,eIF4 A-like helicases, eEF1A and eEF1B, which are required in interacting with viral RNAs and regulating various aspects of the infection cycle,have also been identified. Here, we summarized the mechanisms utilized by RNA viruses of eukaryotic plants and the essential roles of e IFs in virus infection. Moreover, we discussed the potential of e IFs as a target gene in the development of genetic resistance to viruses for crop improvement. This review highlighted newly revealed examples of abnormal translational strategies and provided insights into natural host resistance mechanisms that have been linked to 3 cap-independent translational enhancer activity.
文摘Fatigue failure continues to be a significant challenge in designing structural and mechanical components subjected to repeated and complex loading.While earlier studies mainly examined material properties and how stress affects lifespan,this review offers the first comprehensive,multiscale comparison of strategies that optimize geometry to improve fatigue performance.This includes everything from microscopic features like the shape of graphite nodules to large-scale design elements such as fillets,notches,and overall structural layouts.We analyze and combine various methods,including topology and shape optimization,the ability of additive manufacturing to finetune internal geometries,and reliability-based design approaches.A key new contribution is our proposal of a standard way to evaluate geometry-focused fatigue design,allowing for consistent comparison and encouraging validation across different fields.Furthermore,we highlight important areas for future research,such as incorporating manufacturing flaws,using multiscale models,and integrating machine learning techniques.This work is the first to provide a broad geometric viewpoint in fatigue engineering,laying the groundwork for future design methods that are driven by data and centered on reliability.
文摘The composition of magnesium alloys is greatly associated with initial deposition behavior of electroless Ni-P coatings.Thus,the initial deposition behavior of electroless Ni–P coatings on ZK60 and ME20 alloys was investigated.The results indicated that differences in the alloy compositions significantly influenced the initial deposition process and the adhesive strength,corrosion resistance,and crystal structure.The initial deposition of coatings on ZK60 and ME20 alloys preferentially occurred on the precipitates.The precipitates in ZK60 alloy had higher chemical activity after HF activation and controlled the initial deposition rate of the coating.The initial deposition rate of the coating on ME20 alloy mainly depended on the density of the Mg F2 film formed by HF activation rather than on the precipitates.Owing to differences in the initial deposition process,the coating on ZK60 alloy had higher adhesive strength and better corrosion resistance than that on ME20 alloy.The coatings on ZK60 and ME20 alloys mainly had crystalline structures,and the coating on ME20 alloy had also a slight microcrystalline structure.
文摘BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81974396,No.81874091,No.82072840,and No.82102734)the Natural Science Foundation of Hubei Province(No.2020CFB829)the Health Commission of Hubei Province Scientific Research Project(No.WJ2021F081).
文摘Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.
文摘Revised national tuberculosis control programme in India has limited co-hort-wise information about what happens to patients diagnosed with multidrug resistant TB (MDR-TB). We determined the pre-treatment loss to follow-up (non-initiation of treatment by programme within 6 months of diagnosis) and time from diagnosis to treatment initiation in Bhopal district, central India (2014). Pre-treatment loss to follow-up was 13% (0.95 CI: 7%, 23%), not significantly different from the national estimates (18%) and median time to initiate treatment was seven days, lower than that reported elsewhere in the country. Bhopal was performing well with reference to time to treatment initiation in programmatic settings.
基金supported by National Natural Science Foundation of China(31860490)YNTC funds(2023530000241007 and 2017YN02)+1 种基金Yunnan Daguan Lab(YNDG202302ZY01)CLZ is supported by the Postdoctoral Fellowship Program of CPSF under grant number GZC20241527。
文摘Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise of resistance-breaking(RB)strains and emerging potyviral species necessitates the development of more durable and broad-spectrum resistance strategies.In this study,our field survey in Yunnan,China,identified potato virus Y(PVY)RB isolates,as well as the prevalence of tobacco vein banding mosaic virus(TVBMV)and chilli veinal mottle virus(ChiVMV),in tobacco carrying the recessive va locus,which lacks the eIF4E1-S susceptibility gene,due to a chromosomal deletion.Protein interaction and viral infection assays demonstrated that both eIF4E1-S and eIFiso4E-T are used by PVY RB as susceptibility factors for infection,with the combined inactivation of these genes confering durable resistance.Similarly,the knockout of eIFiso4E-S,in the va genetic background,provided effective resistance to TVBMV and reduced susceptibility to ChiVMV.Notably,pyramiding mutations in eIFiso4E-S and eIFiso4E-T,in va tobacco,generated plants exhibiting robust,broad-spectrum resistance,to all three viruses,without compromising plant development.These findings underscore the potential of stacking eIF4E mutations to engineer durable,broad-spectrum resistance to potyviruses in tobacco,offering a promising strategy for crop improvement.
基金Supported by Natural Science Foundation of Hubei Province,No.2016CFB596Wuhan City Medical Research Project,Nos.WX15B14and WX17Q39Hubei Province Scientific Research Project,No.WJ2015MB137
文摘Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers.Accumulated evidence shows that eIF5A2 initiates tumor formation,enhances cancer cell growth,increases cancer cell metastasis,and promotes treatment resistance through multiple means,including inducing epithelial–mesenchymal transition,cytoskeletal rearrangement,angiogenesis,and metabolic reprogramming.Expression of eIF5A2 in cancer correlates with poor survival,advanced disease stage,as well as metastasis,suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis.All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target.This review focuses on the expression,subcellular localization,post-translational modifications,and regulatory networks of eIF5A2,as well as its biochemical functions and evolving clinical applications in cancer,especially in human digestive system neoplasms.
文摘In beam-to-column joint with bolted end-plate connection,the structural details of column flange reinforced by backing plate and column web panel reinforced by supplementary plate are analyzed.The joint is divided into some basic components,and the initial stiffness of each component is obtained.Especially,the initial stiffness of reinforced components is drawn by theoretical model and finite element analysis.The initial stiffness of reinforced joint can be obtained by assembling the initial stiffness of each component.The design moment resistance of column flange reinforced by backing plate is deduced based on yield line method,and the design moment resistances of other components are deduced based on present codes.The design moment resistance of the reinforced joint is then determined by the minimum of the design moment resistances of all components.By comparison with the results of finite element calculation,it is verified that the method to calculate the initial stiffness of reinforced joint is accurate enough to be used to estimate the rigid behavior of the joint and to make parametric study.
基金Funded by the National Natural Science Foundation of China(No.52172007)。
文摘To analyze the impact of bubbles on the mechanical behavior of glasses,by controlling the refining time,we prepared three borosilicate glasses with the same composition and different porosity.By the analysis software integrated within the optical microscope,the diameter and number of the bubbles on the surface of three borosilicate glasses were quantified.From the hardness and crack initiation resistance(CR),we built the relationship between the porosity and the mechanical performance of these borosilicate glasses.
