While variable regions of immunoglobulins are extensively diversified by V(D)J recombination and somatic hypermutation in vertebrates,the constant regions of immunoglobulin heavy chains also utilize certain mechanisms...While variable regions of immunoglobulins are extensively diversified by V(D)J recombination and somatic hypermutation in vertebrates,the constant regions of immunoglobulin heavy chains also utilize certain mechanisms to produce diversity,including class switch recombination(CSR),subclass differentiation,and alternative expression of the same gene.Many species of birds,reptiles,and amphibians express a truncated isoform of immunoglobulin Y(IgY),termed IgY(ΔFc),which lacks theυCH3 andυCH4 domains.In Anseriformes,IgY(ΔFc)arises from alternative transcriptional termination sites within the sameυgene,whereas in some turtles,intact IgY and IgY(ΔFc)are encoded by distinct genes.Different from the previously reported IgY(ΔFc)variants,this study identified a truncated IgY in the snake Elaphe taeniura,characterized by the loss of only a portion of the CH4 domain.Western blotting and liquid chromatographytandem mass spectrometry confirmed that this truncated IgY is generated by post-translational cleavage at N338 within the IgY heavy chain constant(CH)region.Furthermore,both human and snake asparaginyl endopeptidase were shown to cleave snake IgY in vitro.These findings reveal a novel mechanism for the production of shortened IgY forms,demonstrating that the immunoglobulin CH region undergoes diversification through distinct strategies across vertebrates.展开更多
Mutations in the cyclin-dependent kinase-like 5 gene(CDKL5)cause a severe neurodevelopmental disorder,yet the impact of truncating mutations remains unclear.Here,we introduce the Cdkl5^(492stop) mouse model,mimicking ...Mutations in the cyclin-dependent kinase-like 5 gene(CDKL5)cause a severe neurodevelopmental disorder,yet the impact of truncating mutations remains unclear.Here,we introduce the Cdkl5^(492stop) mouse model,mimicking C-terminal truncating mutations in patients.492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors,alongside other behavioral deficits.After creating cell lines with various Cdkl5 truncating mutations,we found that these mutations are regulated by the nonsense-mediated RNA decay pathway.Most truncating mutations result in CDKL5 protein loss,leading to multiple disease phenotypes,and offering new insights into the pathogenesis of CDKL5 disorder.展开更多
In this study,the truncated octahedral CeO_(2)(CeO_(2)-to)with special morphology was prepared by the solvothermal method with oleic acid(OA)and oleamine(OM)as the morphology-directing agents.High-resolution transmiss...In this study,the truncated octahedral CeO_(2)(CeO_(2)-to)with special morphology was prepared by the solvothermal method with oleic acid(OA)and oleamine(OM)as the morphology-directing agents.High-resolution transmission electron microscopy(HRTEM)results show that CeO_(2)-to exposes composite{100}and{111}facets,while CeO_(2)cubic(CeO_(2)-c)and CeO_(2)octahedral(CeO_(2)-o)only expose single crystal facets of{100}plane and{111}plane,respectively.Interestingly,this CeO_(2)-to photocatalyst exhibits remarkable photooxidation performance of gaseous acetaldehyde(CH_(3)CHO)degradation,in which CO_(2)generation value reaches 1.78 and 7.97-times greater than that of CeO_(2)-c and CeO_(2)-o,respectively.In addition,the active species trapping experiment signifies that superoxide(·O_(2)^(-))and holes(h^(+))are the main reactive substances during the CH_(3)CHO degradation process,and the electron paramagnetic resonance(EPR)spectra indicates that the former is the major contributor.Notably,the electron transfer mechanism between CeO_(2)-to{100}and{111}facets and the surface oxygen adsorption ability are revealed via density functional theory(DFT)calculations.It is also confirmed that{100}facets are more conducive to the absorption of acetaldehyde than{111}facets.Finally,a reasonable mechanism for improved photocatalytic CH_(3)CHO degradation on CeO_(2)-to is proposed based on relevant experiments and DFT calculations.This study demonstrates that the systematic development of surface homojunction structured photocatalysts can efficiently increase the degradation activity for volatile organic compounds(VOCs).It also offers additional direction for optimizing the photocatalytic activity of other ceriumbased photocatalysts.展开更多
This paper focuses on the continuity of the truncated Hardy-Littlewood maximal function.We first show that the truncated Hardy-Littlewood maximal function is lower semi-continuous.Then by investigating the behavior of...This paper focuses on the continuity of the truncated Hardy-Littlewood maximal function.We first show that the truncated Hardy-Littlewood maximal function is lower semi-continuous.Then by investigating the behavior of the truncated Hardy-Littlewood maximal function when the truncated parameterγchanges,we obtain an equivalent condition of the continuity of the truncated Hardy-Littlewood maximal function.展开更多
This paper investigates the hydrodynamic characteristics of floating truncated cylinders undergoing horizontal and vertical motions due to earthquake excitations in the finite water depth.The governing equation of the...This paper investigates the hydrodynamic characteristics of floating truncated cylinders undergoing horizontal and vertical motions due to earthquake excitations in the finite water depth.The governing equation of the hydrodynamic pressure acting on the cylinder is derived based on the radiation theory with the inviscid and incompressible assumptions.The governing equation is solved by using the method of separating variables and analytical solutions are obtained by assigning reasonable boundary conditions.The analytical result is validated by a numerical model using the exact artificial boundary simulation of the infinite water.The main variation and distribution characteristics of the hydrodynamic pressure acting on the side and bottom of the cylinder are analyzed for different combinations of wide-height and immersion ratios.The added mass coefficient of the cylinder is calculated by integrating the hydrodynamic pressure and simplified formulas are proposed for engineering applications.The calculation results show that the simplified formulas are in good agreement with the analytical solutions.展开更多
CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozy...CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozygous mutants of the insulin receptor gene 2(NlInR2)in the brown planthopper(Nilaparvata lugens)using CRISPR/Cas9 genome editing.Both frameshift mutants,E5_D17 and E6_I7,differentiated towards long wings,but there were differences in wing morphology,with E5_D17 showing wing deformities.Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants,as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17.Additionally,the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein.RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%,suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions.Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.展开更多
This study presents the design of a modified attributed control chart based on a double sampling(DS)np chart applied in combination with generalized multiple dependent state(GMDS)sampling to monitor the mean life of t...This study presents the design of a modified attributed control chart based on a double sampling(DS)np chart applied in combination with generalized multiple dependent state(GMDS)sampling to monitor the mean life of the product based on the time truncated life test employing theWeibull distribution.The control chart developed supports the examination of the mean lifespan variation for a particular product in the process of manufacturing.Three control limit levels are used:the warning control limit,inner control limit,and outer control limit.Together,they enhance the capability for variation detection.A genetic algorithm can be used for optimization during the in-control process,whereby the optimal parameters can be established for the proposed control chart.The control chart performance is assessed using the average run length,while the influence of the model parameters upon the control chart solution is assessed via sensitivity analysis based on an orthogonal experimental design withmultiple linear regression.A comparative study was conducted based on the out-of-control average run length,in which the developed control chart offered greater sensitivity in the detection of process shifts while making use of smaller samples on average than is the case for existing control charts.Finally,to exhibit the utility of the developed control chart,this paper presents its application using simulated data with parameters drawn from the real set of data.展开更多
Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosph...Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression.To evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor tissues.We established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer assays.Instead,there is no response from the responder.Furthermore,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell migration.We found that quercetin effectively reduced t-DARPP expression in HER2+BC cells.In t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest.In conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.展开更多
Phospholipase A1(PLA1)is a kind of specific phospholipid hydrolase widely used in food,medical,textile.However,limitations in its expression and enzymatic activity have prompted the investigation of the phospholipase-...Phospholipase A1(PLA1)is a kind of specific phospholipid hydrolase widely used in food,medical,textile.However,limitations in its expression and enzymatic activity have prompted the investigation of the phospholipase-assisting protein PlaS.In this study,we elucidate the role of PlaS in enhancing the expression and activity of PlaA1 through N-terminal truncation.Our research demonstrates that truncating the N-terminal region of PlaS effectively overcomes its inhibitory effect on host cells,resulting in improved cell growth and increased protein solubility of the protein.The yeast two-hybrid assay confirms the interaction between PlaA1 and N-terminal truncated PlaS(ΔN27 PlaS),highlighting their binding capabilities.Furthermore,in vitro studies using Biacore analysis reveal a concentration-dependent and specific binding between PlaA1 andΔN27 PlaS,exhibiting high affinity.Molecular docking analysis provides insights into the hydrogen bond interactions betweenΔN27 PlaS and PlaA1,identifying key amino acid residues crucial for their binding.Finally,the enzyme activity of PLA1 was boost to 8.4 U/mL by orthogonal test.Study significantly contributes to the understanding of the interaction mechanism between PlaS and PlaA1,offering potential strategies for enhancing PlaA1 activity through protein engineering approaches.展开更多
基金supported by the Fundamental Research Funds for the Central Universities,Southwest Minzu University(ZYN2023097)Scientific and Technological Innovation Team for Qinghai-Xizang Plateau Research in Southwest Minzu University(2024CXTD13)。
文摘While variable regions of immunoglobulins are extensively diversified by V(D)J recombination and somatic hypermutation in vertebrates,the constant regions of immunoglobulin heavy chains also utilize certain mechanisms to produce diversity,including class switch recombination(CSR),subclass differentiation,and alternative expression of the same gene.Many species of birds,reptiles,and amphibians express a truncated isoform of immunoglobulin Y(IgY),termed IgY(ΔFc),which lacks theυCH3 andυCH4 domains.In Anseriformes,IgY(ΔFc)arises from alternative transcriptional termination sites within the sameυgene,whereas in some turtles,intact IgY and IgY(ΔFc)are encoded by distinct genes.Different from the previously reported IgY(ΔFc)variants,this study identified a truncated IgY in the snake Elaphe taeniura,characterized by the loss of only a portion of the CH4 domain.Western blotting and liquid chromatographytandem mass spectrometry confirmed that this truncated IgY is generated by post-translational cleavage at N338 within the IgY heavy chain constant(CH)region.Furthermore,both human and snake asparaginyl endopeptidase were shown to cleave snake IgY in vitro.These findings reveal a novel mechanism for the production of shortened IgY forms,demonstrating that the immunoglobulin CH region undergoes diversification through distinct strategies across vertebrates.
基金supported by the Innovation of Science and Technology 2030-Major Project"Platform of Nonhuman Primate Models"(2021ZD0200900)the Ministry of Science and Technology(2018YFA0801404)+1 种基金the National Natural Science Foundation of China(82021001)the Shanghai Municipal Science and Technology Major Project.
文摘Mutations in the cyclin-dependent kinase-like 5 gene(CDKL5)cause a severe neurodevelopmental disorder,yet the impact of truncating mutations remains unclear.Here,we introduce the Cdkl5^(492stop) mouse model,mimicking C-terminal truncating mutations in patients.492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors,alongside other behavioral deficits.After creating cell lines with various Cdkl5 truncating mutations,we found that these mutations are regulated by the nonsense-mediated RNA decay pathway.Most truncating mutations result in CDKL5 protein loss,leading to multiple disease phenotypes,and offering new insights into the pathogenesis of CDKL5 disorder.
基金supported by the National Natural Science Foundation of China(Nos.21805191 and 22205084)Project funded by China Postdoctoral Science Foundation(No.2023M741039)+3 种基金Project funded by National&Local Joint Engineering Research Center for Mineral Salt Deep Utilization(SF202303)Project Funded by Yangzhou University(137013308),Guangdong Basic and Applied Basic Research Foundation(No.2020A1515010982)Shenzhen Stable Support Project(No.20200812122947002),the Innovative Science and Technology Platform Project of Cooperation between Yangzhou City and Yangzhou UniversityPostgraduate Research&Practice Innovation Program of Jiangsu Province(Yangzhou University,No.XKYCX20_014)。
文摘In this study,the truncated octahedral CeO_(2)(CeO_(2)-to)with special morphology was prepared by the solvothermal method with oleic acid(OA)and oleamine(OM)as the morphology-directing agents.High-resolution transmission electron microscopy(HRTEM)results show that CeO_(2)-to exposes composite{100}and{111}facets,while CeO_(2)cubic(CeO_(2)-c)and CeO_(2)octahedral(CeO_(2)-o)only expose single crystal facets of{100}plane and{111}plane,respectively.Interestingly,this CeO_(2)-to photocatalyst exhibits remarkable photooxidation performance of gaseous acetaldehyde(CH_(3)CHO)degradation,in which CO_(2)generation value reaches 1.78 and 7.97-times greater than that of CeO_(2)-c and CeO_(2)-o,respectively.In addition,the active species trapping experiment signifies that superoxide(·O_(2)^(-))and holes(h^(+))are the main reactive substances during the CH_(3)CHO degradation process,and the electron paramagnetic resonance(EPR)spectra indicates that the former is the major contributor.Notably,the electron transfer mechanism between CeO_(2)-to{100}and{111}facets and the surface oxygen adsorption ability are revealed via density functional theory(DFT)calculations.It is also confirmed that{100}facets are more conducive to the absorption of acetaldehyde than{111}facets.Finally,a reasonable mechanism for improved photocatalytic CH_(3)CHO degradation on CeO_(2)-to is proposed based on relevant experiments and DFT calculations.This study demonstrates that the systematic development of surface homojunction structured photocatalysts can efficiently increase the degradation activity for volatile organic compounds(VOCs).It also offers additional direction for optimizing the photocatalytic activity of other ceriumbased photocatalysts.
基金Supported by NSF of Zhejiang Province of China(LQ18A010002,LQ17A010002)。
文摘This paper focuses on the continuity of the truncated Hardy-Littlewood maximal function.We first show that the truncated Hardy-Littlewood maximal function is lower semi-continuous.Then by investigating the behavior of the truncated Hardy-Littlewood maximal function when the truncated parameterγchanges,we obtain an equivalent condition of the continuity of the truncated Hardy-Littlewood maximal function.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.52078010 and 52101321)the National Key Research and Development Program of China(Grant No.2022YFC3004300).
文摘This paper investigates the hydrodynamic characteristics of floating truncated cylinders undergoing horizontal and vertical motions due to earthquake excitations in the finite water depth.The governing equation of the hydrodynamic pressure acting on the cylinder is derived based on the radiation theory with the inviscid and incompressible assumptions.The governing equation is solved by using the method of separating variables and analytical solutions are obtained by assigning reasonable boundary conditions.The analytical result is validated by a numerical model using the exact artificial boundary simulation of the infinite water.The main variation and distribution characteristics of the hydrodynamic pressure acting on the side and bottom of the cylinder are analyzed for different combinations of wide-height and immersion ratios.The added mass coefficient of the cylinder is calculated by integrating the hydrodynamic pressure and simplified formulas are proposed for engineering applications.The calculation results show that the simplified formulas are in good agreement with the analytical solutions.
基金the National Natural Science Foundation of China(31730073).
文摘CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozygous mutants of the insulin receptor gene 2(NlInR2)in the brown planthopper(Nilaparvata lugens)using CRISPR/Cas9 genome editing.Both frameshift mutants,E5_D17 and E6_I7,differentiated towards long wings,but there were differences in wing morphology,with E5_D17 showing wing deformities.Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants,as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17.Additionally,the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein.RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%,suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions.Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.
基金the Science,Research and Innovation Promotion Funding(TSRI)(Grant No.FRB660012/0168)managed under Rajamangala University of Technology Thanyaburi(FRB66E0646O.4).
文摘This study presents the design of a modified attributed control chart based on a double sampling(DS)np chart applied in combination with generalized multiple dependent state(GMDS)sampling to monitor the mean life of the product based on the time truncated life test employing theWeibull distribution.The control chart developed supports the examination of the mean lifespan variation for a particular product in the process of manufacturing.Three control limit levels are used:the warning control limit,inner control limit,and outer control limit.Together,they enhance the capability for variation detection.A genetic algorithm can be used for optimization during the in-control process,whereby the optimal parameters can be established for the proposed control chart.The control chart performance is assessed using the average run length,while the influence of the model parameters upon the control chart solution is assessed via sensitivity analysis based on an orthogonal experimental design withmultiple linear regression.A comparative study was conducted based on the out-of-control average run length,in which the developed control chart offered greater sensitivity in the detection of process shifts while making use of smaller samples on average than is the case for existing control charts.Finally,to exhibit the utility of the developed control chart,this paper presents its application using simulated data with parameters drawn from the real set of data.
基金The National Science and Technology Council of Taiwan funded this study.
文摘Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression.To evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor tissues.We established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer assays.Instead,there is no response from the responder.Furthermore,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell migration.We found that quercetin effectively reduced t-DARPP expression in HER2+BC cells.In t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest.In conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.
基金financially supported by National Natural Science Foundations of China(No.31471615)Scientific Research Start-up Fund for Introduced Talents of Anhui Polytechnic University(2022YOO068)Natural Science Research Project of Colleges and Universities in Anhui Province(Grant 2022AH050971).
文摘Phospholipase A1(PLA1)is a kind of specific phospholipid hydrolase widely used in food,medical,textile.However,limitations in its expression and enzymatic activity have prompted the investigation of the phospholipase-assisting protein PlaS.In this study,we elucidate the role of PlaS in enhancing the expression and activity of PlaA1 through N-terminal truncation.Our research demonstrates that truncating the N-terminal region of PlaS effectively overcomes its inhibitory effect on host cells,resulting in improved cell growth and increased protein solubility of the protein.The yeast two-hybrid assay confirms the interaction between PlaA1 and N-terminal truncated PlaS(ΔN27 PlaS),highlighting their binding capabilities.Furthermore,in vitro studies using Biacore analysis reveal a concentration-dependent and specific binding between PlaA1 andΔN27 PlaS,exhibiting high affinity.Molecular docking analysis provides insights into the hydrogen bond interactions betweenΔN27 PlaS and PlaA1,identifying key amino acid residues crucial for their binding.Finally,the enzyme activity of PLA1 was boost to 8.4 U/mL by orthogonal test.Study significantly contributes to the understanding of the interaction mechanism between PlaS and PlaA1,offering potential strategies for enhancing PlaA1 activity through protein engineering approaches.
