Alarm flood is one of the main problems in the alarm systems of industrial process. Alarm root-cause analysis and alarm prioritization are good for alarm flood reduction. This paper proposes a systematic rationalizati...Alarm flood is one of the main problems in the alarm systems of industrial process. Alarm root-cause analysis and alarm prioritization are good for alarm flood reduction. This paper proposes a systematic rationalization method for multivariate correlated alarms to realize the root cause analysis and alarm prioritization. An information fusion based interpretive structural model is constructed according to the data-driven partial correlation coefficient calculation and process knowledge modification. This hierarchical multi-layer model is helpful in abnormality propagation path identification and root-cause analysis. Revised Likert scale method is adopted to determine the alarm priority and reduce the blindness of alarm handling. As a case study, the Tennessee Eastman process is utilized to show the effectiveness and validity of proposed approach. Alarm system performance comparison shows that our rationalization methodology can reduce the alarm flood to some extent and improve the performance.展开更多
Based on the classic diffusion controlled nucleation and goth theory, the sympathatic nucleation- ledgewise growth mechanism of bainite was studied theoretically for low carbon Fe-C alloys. The rationality of the occu...Based on the classic diffusion controlled nucleation and goth theory, the sympathatic nucleation- ledgewise growth mechanism of bainite was studied theoretically for low carbon Fe-C alloys. The rationality of the occurrence of sympathetic nucleation on the terraces of ledges compating with lateral ledge growth and other sites nucleation was demonstrated by the present work quantita- tively The calculations indicated that low reaction temperatures and high carbon concentrations may favor the sympathetic nucleation, thus accounting for the formation of multilayer structures of bainite.展开更多
Shanxi Province is a typical resource-based region. After years of economic transformation, the air quality has been at a low level for a long time. The rationalization of industrial structure can measure the effect o...Shanxi Province is a typical resource-based region. After years of economic transformation, the air quality has been at a low level for a long time. The rationalization of industrial structure can measure the effect of economic transformation and whether it has an important impact on air quality. Therefore, it is necessary to study the non-linear impact that the rationalization of industrial structure has had on air quality at different stages, which is of positive significance for the continuing transformation and upgrading of resource-based regions. This study constructs a threshold regression model based on the panel data of 11 provincial cities in Shanxi Province from 2004 to 2016. The results show that the rationalization of industrial structure had a double threshold effect on air quality under different threshold variables. On the whole, optimizing the rationalization of industrial structure in Shanxi Province can improve air quality, and the improvement effect dropped first, and then began to rise. As a result, the current energy transformation and upgrading process should focus on the rationalization of industrial structure to solve the conflict between air quality and economic development.展开更多
The Beijing-Tianjin-Hebei region is one of the regions with the most dynamic economies,highest degrees of openness,strongest innovation capacities and largest populations,as well as an important engine driving China’...The Beijing-Tianjin-Hebei region is one of the regions with the most dynamic economies,highest degrees of openness,strongest innovation capacities and largest populations,as well as an important engine driving China’s economic development.Currently,the development of the BeijingTianjin-Hebei region faces many difficulties,including an inefficient distribution of regional functions,imbalance in industrial structure,low sophistication,and serious overburdening of resources and the environment.Promoting the overall coordinated development of the region has become an urgent challenge.In this paper,according to the conventions of industrial structure optimization,the three core indicators of regional industrial structure rationalization,sophistication and ecologicalization are constructed.With the help of the grey dynamic correlation model,the three indicators are coupled with the economic growth rate,and the industrial structure optimization index of the Beijing-Tianjin-Hebei region is comprehensively measured.The study shows that rationalization of the industrial structure in the Beijing-Tianjin-Hebei region is increasing but that this trend is not obvious;sophistication of the industrial structure is relatively high and has also been operating at a high level;however,the overall ecological level of the industrial structure in the Beijing-Tianjin-Hebei region is not high and presents the characteristics of high in the middle and low at both ends.In terms of the relationship between industrial structure and economic growth in the Beijing-Tianjin-Hebei region,ecologicalization of the industrial structure has the greatest influence on economic growth,followed by sophistication of the industrial structure,and rationalization of the industrial structure has the weakest influence.展开更多
1 Results Homogeneity of fibroin thin films by pulsed laser deposition (PLD) was significantly improved by introducing autogenous binders to consolidate and homogenize the irradiation targets.Homogenization includes a...1 Results Homogeneity of fibroin thin films by pulsed laser deposition (PLD) was significantly improved by introducing autogenous binders to consolidate and homogenize the irradiation targets.Homogenization includes among others,decreases in the size of nanostructural units and the fractional debris.Simultaneously,the deposition rate was substantially increased.Autogenous binders are prepared via degumming and liquefaction of fibroin by using Na2CO3 and LiBr,respectively.We also found that optically hom...展开更多
Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been d...Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been demonstrated to be one of the most efficient and cost-effective strategies to curb the shuttle effect,and tremendous research progress has been achieved.The efficiency of a separator depends on its interaction with LiPSs,which is governed by the surface energy and binding strength.Despite several review works that have been reported to advance the separators,most of them primarily focus on active material innovation and construction.The most crucial issues of surface binding energy have not been systematically reviewed,limiting the precise design of efficient separators.In this review,fundamentals related to surface energy and binding interactions with LiPSs are comprehensively analyzed and discussed.With surface binding and energy main lines,the advancements in separator engineering strategies are elaborately summarized and discussed.Moreover,techniques for evaluating affinity to LiPSs are thoroughly analyzed to avoid any ambiguities in measurement.Based on the research context,valuable research directions are suggested to construct efficient separators.This work provides guidelines to regulate the surface binding and energy of separators for high-performance LSBs.展开更多
The Double Take column looks at a single topic from an African and Chinese perspective.This month,we discuss how to understand the growing emphasis on emotional returns among young people.Emotional value has emerged a...The Double Take column looks at a single topic from an African and Chinese perspective.This month,we discuss how to understand the growing emphasis on emotional returns among young people.Emotional value has emerged as a central force shaping youth decision-making across work,consumption,relationships and lifestyle choices.Unlike traditional economic rationality that prioritises income and material security,emotional value focuses on how choices make individuals feel and how they align with personal meaning.This shift is particularly evident in rapidly transforming societies such as China and Ghana,where economic restructuring,globalisation and social change have reshaped pathways to adulthood.展开更多
Carotenoid cleavage dioxygenase 4(CCD4)controls the rate-limiting step ofβ-ionone biosynthesis,making it a valuable target for healthcare and pharmaceutical applications.Nicotiana tabacum,a carotenoid-richd crop spec...Carotenoid cleavage dioxygenase 4(CCD4)controls the rate-limiting step ofβ-ionone biosynthesis,making it a valuable target for healthcare and pharmaceutical applications.Nicotiana tabacum,a carotenoid-richd crop species,is a promising source forβ-ionone production.This study aimed to modify CCD4 activity to increaseβ-ionone yield in tobacco.We identified two isoforms of CCD4 in N.tabacum,NtCCD4a and NtCCD4b,with NtCCD4a exhibiting significantly higher expression levels than NtCCD4b.Using solid-phase microextraction gas chromatography-mass spectrometry(SPME-GC–MS),we demonstrated that NtCCD4a effectively catalyzes the cleavage ofβ-carotene to produceβ-ionone.To improve its enzymatic activity,we applied structure-based rational design to reconstruct the active pocket of NtCCD4a,followed by high-throughput screening of mutant variants.Three single base mutants,F181G,F184L,and F337M,in NtCCD4a showed enhancedβ-ionone production compared to the wild-type,with F337M yielding the highest amount.No synergistic effects were observed among the three mutants.Transgenic tobacco plants expressing the F181G,F184L,and F337M mutations had acceleratedβ-carotene cleavage and increasedβ-ionone production relative to the wild-type NtCCD4a.Our results establish a framework for the design of CCD4 in major crop species through genome editing technology.展开更多
The von Hippel-Lindau tumor suppressor(VHL)has been extensively used to develop degraders targeting numerous proteins of interest.However,studies on the rational design of VHL-proteolysis-targeting chimeras(PROTACs)re...The von Hippel-Lindau tumor suppressor(VHL)has been extensively used to develop degraders targeting numerous proteins of interest.However,studies on the rational design of VHL-proteolysis-targeting chimeras(PROTACs)remain scarce.This study aimed to develop strategies to investigate VHL-recruiting PROTACs connecting with varying attachment sites on VHL ligands,which could be utilized for KRAS^(G12C) degraders development and expanded to additional targets.We developed a molecular dynamics(MD)-based strategy to explore the stability of ternary complexes induced by KRAS^(G12C) PROTACs with four distinct attachment sites of VH032.We found a potent degrader namely YN14-H,linked to hydroxyl group on VH032 benzene ring,exhibited the most superior ability of inducing ternary complexes,reflected by the lowest dissociation constant(Kd)for ternary complex induction and the highest AlphaScreen(AS)-based interaction.YN14-H inhibited cell growth with low nanomolar half maximal inhibitory concentration(IC_(50))and half maximal degradation concentration(DC_(50))values as well as>98%of maximum degradation(D_(max))in NCI-H358 and MIA PaCa-2 cells harboring KRAS^(G12C)-mutation.Mechanistically,YN14-H significantly induced apoptosis and inhibited the migratory capacity.Notably,YN14-H demonstrated favorable pharmacokinetic properties and excellent antitumor activity in vivo.Furthermore,bromodomain-containing protein 7(BRD7)and Bruton tyrosine kinase(BTK)degraders attached to distinct sites on VH032 further verified the rationality and universality of our MD-based strategies.Our findings demonstrated that YN14-H could serve as a promising candidate for the treatment of tumors with KRAS^(G12C)-mutation and present a strategy for the rational design of VHL-recruiting PROTACs that target additional proteins at distinct attachment sites.展开更多
From the PersPective of the systemsaPProaeh,the urban eeonomie functions re-fer to the role Played by the eeonomy of theeity in its surrounding areas.Beeause of different geograPhieal loeations,historiealeonditions,th...From the PersPective of the systemsaPProaeh,the urban eeonomie functions re-fer to the role Played by the eeonomy of theeity in its surrounding areas.Beeause of different geograPhieal loeations,historiealeonditions,the various roles and funetionsof the eities in the national economy,theeeonomie funetions of a eity may be of展开更多
We give an overview of five rationalization theories for spaces(Bousfield-Kan’s Q-completion;Sullivan’s rationaliz ation;Bousifeld’s homology rationaliz ation;Casacuberta-Peschke’s Ω-rationalization;Gomez-Tato-Ha...We give an overview of five rationalization theories for spaces(Bousfield-Kan’s Q-completion;Sullivan’s rationaliz ation;Bousifeld’s homology rationaliz ation;Casacuberta-Peschke’s Ω-rationalization;Gomez-Tato-Halperin-Tanré’s π-fiberwise rationalization)that extend the classical rationalization of simply connected spaces.We also give an overview of the corresponding rationalization theories for groups(Q-completion;HQ-localization;Baumslag rationalization)that extend the classical Malcev completion.展开更多
This study investigates the dark side of the non-fungible token(NFT)marketplace,with a focus on understanding the risks,and underlying factors driving fraud in the NFT ecosystem.Using the fraud triangle framework,this...This study investigates the dark side of the non-fungible token(NFT)marketplace,with a focus on understanding the risks,and underlying factors driving fraud in the NFT ecosystem.Using the fraud triangle framework,this study examines pressure,opportunity,and rationalization from individual and organizational perspectives.The research provides a comprehensive understanding of the contributing factors to NFT marketplace fraud by analyzing the reasons behind fraudulent actions.A conceptual framework is developed that includes ten propositions to aid in understanding the complexity of this issue.This study’s outcomes will assist policymakers in crafting efficient approaches to mitigate fraud within the NFT marketplace.展开更多
This research aims to understand the causes of fraud through the approach of the Fraud Triangle Theory,which includes three main factors:pressure,opportunity,rationalization.By using the Systematic Literature Review m...This research aims to understand the causes of fraud through the approach of the Fraud Triangle Theory,which includes three main factors:pressure,opportunity,rationalization.By using the Systematic Literature Review method from various relevant international journals,it analyzed systematically to identify patterns,trends,and theoretical contributions to efforts in detecting and preventing fraud.The results of this study show that the three factors in the Fraud Triangle Theory significantly contribute to the occurrence of fraud.Opportunity as the most dominant factor is caused by weak internal control systems and lack of oversight.In addition,economic pressure,and a permissive organizational environment,as well as the rationalization processes by individuals,also increase the tendency for a person to commit fraud.These findings emphasize the need for a comprehensive approach in fraud prevention strategies,through ethical values,the establishment of an organizational culture with integrity,and the implementation of more effective internal control and oversight.展开更多
Let X be a closed simply connected rationally elliptic 4-manifold.The rational homotopy type of homotopy fixed point sets X^(hS^(1))is determined,and based on some relations between X^(hS^(1))and X^(S^(1)),the rationa...Let X be a closed simply connected rationally elliptic 4-manifold.The rational homotopy type of homotopy fixed point sets X^(hS^(1))is determined,and based on some relations between X^(hS^(1))and X^(S^(1)),the rational homotopy type of the fixed point set X^(S^(1))is determined.展开更多
In the successive rise of the metaverse and artificial intelligence(AI),rationalism and emotionalism have consistently manifested as symptoms of modernity throughout their developmental trajectories.This paper argues ...In the successive rise of the metaverse and artificial intelligence(AI),rationalism and emotionalism have consistently manifested as symptoms of modernity throughout their developmental trajectories.This paper argues that the achievements and crises of both fields signify the triumph of rationalism in the context of deepening modernity,while simultaneously harboring an intrinsic impetus and possibility for transitioning from rationalism to emotionalism.This dynamic serves as a quintessential representation of modernity’s crises and their transcendence.Centered on embodied cognitive science,AI and the metaverse—rooted in rationalism—now face challenges in shifting toward emotionalism,revealing their inadequacy in addressing this shift.Humanity must explore new modernity-deepening paradigms grounded in emotionalism to confront and transcend the potential crises posed by the metaverse and AI.展开更多
Background:Neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ration(PLR)have been shown to contribute to tumour progression and response to therapy.Methods:We retrospectively counted NLR and PLR in 719 patients ...Background:Neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ration(PLR)have been shown to contribute to tumour progression and response to therapy.Methods:We retrospectively counted NLR and PLR in 719 patients with advanced malignancies receiving chemo-and/or immuno-therapy.Results:Both the pretreatment NLR and PLR were significantly elevated in patients with progressive disease than in those without progressive disease.Compared to low groups,the high NLR and PLR groups showed significantly worse event free survival.Conclusion:We propose that NLR and PLR are not only effective blood markers for predicting therapeutic responses to chemo-and/or immuno-therapy,but also useful in detecting survival in diverse malignancies.展开更多
Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeuti...Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.展开更多
Chlorobenzene is a model molecule for researching harmful chlorinated volatile organic compounds.Designing the chemical adsorption site for complex molecules such as chlorobenzene is challenging without a large datase...Chlorobenzene is a model molecule for researching harmful chlorinated volatile organic compounds.Designing the chemical adsorption site for complex molecules such as chlorobenzene is challenging without a large dataset and reasonable descriptors.Here,the adsorption of chlorobenzene on a phosphorylated CeO_(2)catalyst was analyzed using density functional theory calculations.Three different surface phosphate(H_(x)PO_(4))models were constructed and used to adsorb chlorobenzene.An orbital interaction with fully occupied antibonding is found in one of three physical adsorptions.Based on this,the surface sites of a tri-cluster(M_(3))located at the CeO_(2)surface have been suggested to activate chlorobenzene.Three different clusters have been tested,namely Fe_(3),Ru_(3),and B_(3).All these clusters can activate and twist chlorobenzene by donating electrons.Fe_(3)and Ru_(3)form bonds with weak covalent and strong ionic characters,while B3forms strong covalent bonds between boron and carbon.This work not only predicts a class of sites for chlorobenzene activation that may prevent polychlorinated by-products but also gives a template for catalyst rational design according to fundamental catalytic theory.展开更多
基金Supported by the National Natural Science Foundation of China(61473026,61104131)the Fundamental Research Funds for the Central Universities(JD1413)
文摘Alarm flood is one of the main problems in the alarm systems of industrial process. Alarm root-cause analysis and alarm prioritization are good for alarm flood reduction. This paper proposes a systematic rationalization method for multivariate correlated alarms to realize the root cause analysis and alarm prioritization. An information fusion based interpretive structural model is constructed according to the data-driven partial correlation coefficient calculation and process knowledge modification. This hierarchical multi-layer model is helpful in abnormality propagation path identification and root-cause analysis. Revised Likert scale method is adopted to determine the alarm priority and reduce the blindness of alarm handling. As a case study, the Tennessee Eastman process is utilized to show the effectiveness and validity of proposed approach. Alarm system performance comparison shows that our rationalization methodology can reduce the alarm flood to some extent and improve the performance.
文摘Based on the classic diffusion controlled nucleation and goth theory, the sympathatic nucleation- ledgewise growth mechanism of bainite was studied theoretically for low carbon Fe-C alloys. The rationality of the occurrence of sympathetic nucleation on the terraces of ledges compating with lateral ledge growth and other sites nucleation was demonstrated by the present work quantita- tively The calculations indicated that low reaction temperatures and high carbon concentrations may favor the sympathetic nucleation, thus accounting for the formation of multilayer structures of bainite.
基金The National Natural Science Foundation of China(71774105)The National Social Science Foundation of China(19BTJ053)+1 种基金The Soft Science Research Project in Shanxi Province of China(2019041012-4)The Institutions of Higher Learning in Shanxi Province Key Research Base of Humanities and Social Sciences Fund Project(2017324).
文摘Shanxi Province is a typical resource-based region. After years of economic transformation, the air quality has been at a low level for a long time. The rationalization of industrial structure can measure the effect of economic transformation and whether it has an important impact on air quality. Therefore, it is necessary to study the non-linear impact that the rationalization of industrial structure has had on air quality at different stages, which is of positive significance for the continuing transformation and upgrading of resource-based regions. This study constructs a threshold regression model based on the panel data of 11 provincial cities in Shanxi Province from 2004 to 2016. The results show that the rationalization of industrial structure had a double threshold effect on air quality under different threshold variables. On the whole, optimizing the rationalization of industrial structure in Shanxi Province can improve air quality, and the improvement effect dropped first, and then began to rise. As a result, the current energy transformation and upgrading process should focus on the rationalization of industrial structure to solve the conflict between air quality and economic development.
基金Supported by the Beijing Municipal Natural Science Foundation of China(9192001,9202002).
文摘The Beijing-Tianjin-Hebei region is one of the regions with the most dynamic economies,highest degrees of openness,strongest innovation capacities and largest populations,as well as an important engine driving China’s economic development.Currently,the development of the BeijingTianjin-Hebei region faces many difficulties,including an inefficient distribution of regional functions,imbalance in industrial structure,low sophistication,and serious overburdening of resources and the environment.Promoting the overall coordinated development of the region has become an urgent challenge.In this paper,according to the conventions of industrial structure optimization,the three core indicators of regional industrial structure rationalization,sophistication and ecologicalization are constructed.With the help of the grey dynamic correlation model,the three indicators are coupled with the economic growth rate,and the industrial structure optimization index of the Beijing-Tianjin-Hebei region is comprehensively measured.The study shows that rationalization of the industrial structure in the Beijing-Tianjin-Hebei region is increasing but that this trend is not obvious;sophistication of the industrial structure is relatively high and has also been operating at a high level;however,the overall ecological level of the industrial structure in the Beijing-Tianjin-Hebei region is not high and presents the characteristics of high in the middle and low at both ends.In terms of the relationship between industrial structure and economic growth in the Beijing-Tianjin-Hebei region,ecologicalization of the industrial structure has the greatest influence on economic growth,followed by sophistication of the industrial structure,and rationalization of the industrial structure has the weakest influence.
文摘1 Results Homogeneity of fibroin thin films by pulsed laser deposition (PLD) was significantly improved by introducing autogenous binders to consolidate and homogenize the irradiation targets.Homogenization includes among others,decreases in the size of nanostructural units and the fractional debris.Simultaneously,the deposition rate was substantially increased.Autogenous binders are prepared via degumming and liquefaction of fibroin by using Na2CO3 and LiBr,respectively.We also found that optically hom...
基金supported by the National Natural Science Foundation of China (52172228)the Natural Science Foundation of Fujian Province (2024J01475 and 2023J05127)
文摘Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been demonstrated to be one of the most efficient and cost-effective strategies to curb the shuttle effect,and tremendous research progress has been achieved.The efficiency of a separator depends on its interaction with LiPSs,which is governed by the surface energy and binding strength.Despite several review works that have been reported to advance the separators,most of them primarily focus on active material innovation and construction.The most crucial issues of surface binding energy have not been systematically reviewed,limiting the precise design of efficient separators.In this review,fundamentals related to surface energy and binding interactions with LiPSs are comprehensively analyzed and discussed.With surface binding and energy main lines,the advancements in separator engineering strategies are elaborately summarized and discussed.Moreover,techniques for evaluating affinity to LiPSs are thoroughly analyzed to avoid any ambiguities in measurement.Based on the research context,valuable research directions are suggested to construct efficient separators.This work provides guidelines to regulate the surface binding and energy of separators for high-performance LSBs.
文摘The Double Take column looks at a single topic from an African and Chinese perspective.This month,we discuss how to understand the growing emphasis on emotional returns among young people.Emotional value has emerged as a central force shaping youth decision-making across work,consumption,relationships and lifestyle choices.Unlike traditional economic rationality that prioritises income and material security,emotional value focuses on how choices make individuals feel and how they align with personal meaning.This shift is particularly evident in rapidly transforming societies such as China and Ghana,where economic restructuring,globalisation and social change have reshaped pathways to adulthood.
基金funded High-Level Talents project of Henan Agricultural University(111-30501301)Project of the National key R&D Program of China(2021YFA0909600)+3 种基金Natural Science Foundation of Henan Province(242300420141)the China Postdoctoral Science Foundation(2020M672308)Cultivation Program for Young Backbone Teachers at Henan University of Technology(DC 11)Science Project 110202101042(JY 19)/2022530000241007,110202102033,110202202038.
文摘Carotenoid cleavage dioxygenase 4(CCD4)controls the rate-limiting step ofβ-ionone biosynthesis,making it a valuable target for healthcare and pharmaceutical applications.Nicotiana tabacum,a carotenoid-richd crop species,is a promising source forβ-ionone production.This study aimed to modify CCD4 activity to increaseβ-ionone yield in tobacco.We identified two isoforms of CCD4 in N.tabacum,NtCCD4a and NtCCD4b,with NtCCD4a exhibiting significantly higher expression levels than NtCCD4b.Using solid-phase microextraction gas chromatography-mass spectrometry(SPME-GC–MS),we demonstrated that NtCCD4a effectively catalyzes the cleavage ofβ-carotene to produceβ-ionone.To improve its enzymatic activity,we applied structure-based rational design to reconstruct the active pocket of NtCCD4a,followed by high-throughput screening of mutant variants.Three single base mutants,F181G,F184L,and F337M,in NtCCD4a showed enhancedβ-ionone production compared to the wild-type,with F337M yielding the highest amount.No synergistic effects were observed among the three mutants.Transgenic tobacco plants expressing the F181G,F184L,and F337M mutations had acceleratedβ-carotene cleavage and increasedβ-ionone production relative to the wild-type NtCCD4a.Our results establish a framework for the design of CCD4 in major crop species through genome editing technology.
基金supported by National Natural Science Foundation of China(No.82404417)State Key Laboratory of National Security Specially Needed Medicines Program(No.LTMC2022Zz006).
文摘The von Hippel-Lindau tumor suppressor(VHL)has been extensively used to develop degraders targeting numerous proteins of interest.However,studies on the rational design of VHL-proteolysis-targeting chimeras(PROTACs)remain scarce.This study aimed to develop strategies to investigate VHL-recruiting PROTACs connecting with varying attachment sites on VHL ligands,which could be utilized for KRAS^(G12C) degraders development and expanded to additional targets.We developed a molecular dynamics(MD)-based strategy to explore the stability of ternary complexes induced by KRAS^(G12C) PROTACs with four distinct attachment sites of VH032.We found a potent degrader namely YN14-H,linked to hydroxyl group on VH032 benzene ring,exhibited the most superior ability of inducing ternary complexes,reflected by the lowest dissociation constant(Kd)for ternary complex induction and the highest AlphaScreen(AS)-based interaction.YN14-H inhibited cell growth with low nanomolar half maximal inhibitory concentration(IC_(50))and half maximal degradation concentration(DC_(50))values as well as>98%of maximum degradation(D_(max))in NCI-H358 and MIA PaCa-2 cells harboring KRAS^(G12C)-mutation.Mechanistically,YN14-H significantly induced apoptosis and inhibited the migratory capacity.Notably,YN14-H demonstrated favorable pharmacokinetic properties and excellent antitumor activity in vivo.Furthermore,bromodomain-containing protein 7(BRD7)and Bruton tyrosine kinase(BTK)degraders attached to distinct sites on VH032 further verified the rationality and universality of our MD-based strategies.Our findings demonstrated that YN14-H could serve as a promising candidate for the treatment of tumors with KRAS^(G12C)-mutation and present a strategy for the rational design of VHL-recruiting PROTACs that target additional proteins at distinct attachment sites.
文摘From the PersPective of the systemsaPProaeh,the urban eeonomie functions re-fer to the role Played by the eeonomy of theeity in its surrounding areas.Beeause of different geograPhieal loeations,historiealeonditions,the various roles and funetionsof the eities in the national economy,theeeonomie funetions of a eity may be of
基金Supported by the Ministry of Science and Higher Education of the Russian Federation,agreement 075-15-2019-1619。
文摘We give an overview of five rationalization theories for spaces(Bousfield-Kan’s Q-completion;Sullivan’s rationaliz ation;Bousifeld’s homology rationaliz ation;Casacuberta-Peschke’s Ω-rationalization;Gomez-Tato-Halperin-Tanré’s π-fiberwise rationalization)that extend the classical rationalization of simply connected spaces.We also give an overview of the corresponding rationalization theories for groups(Q-completion;HQ-localization;Baumslag rationalization)that extend the classical Malcev completion.
文摘This study investigates the dark side of the non-fungible token(NFT)marketplace,with a focus on understanding the risks,and underlying factors driving fraud in the NFT ecosystem.Using the fraud triangle framework,this study examines pressure,opportunity,and rationalization from individual and organizational perspectives.The research provides a comprehensive understanding of the contributing factors to NFT marketplace fraud by analyzing the reasons behind fraudulent actions.A conceptual framework is developed that includes ten propositions to aid in understanding the complexity of this issue.This study’s outcomes will assist policymakers in crafting efficient approaches to mitigate fraud within the NFT marketplace.
文摘This research aims to understand the causes of fraud through the approach of the Fraud Triangle Theory,which includes three main factors:pressure,opportunity,rationalization.By using the Systematic Literature Review method from various relevant international journals,it analyzed systematically to identify patterns,trends,and theoretical contributions to efforts in detecting and preventing fraud.The results of this study show that the three factors in the Fraud Triangle Theory significantly contribute to the occurrence of fraud.Opportunity as the most dominant factor is caused by weak internal control systems and lack of oversight.In addition,economic pressure,and a permissive organizational environment,as well as the rationalization processes by individuals,also increase the tendency for a person to commit fraud.These findings emphasize the need for a comprehensive approach in fraud prevention strategies,through ethical values,the establishment of an organizational culture with integrity,and the implementation of more effective internal control and oversight.
文摘Let X be a closed simply connected rationally elliptic 4-manifold.The rational homotopy type of homotopy fixed point sets X^(hS^(1))is determined,and based on some relations between X^(hS^(1))and X^(S^(1)),the rational homotopy type of the fixed point set X^(S^(1))is determined.
基金supported by the China Metaverse and Digital Talent Development Initiative and the general project of the National Social Science Foundation of China titled“Theoretical Interpretation of Advertising Messaging and the Development of a Typical Case Database”(19BXW085).
文摘In the successive rise of the metaverse and artificial intelligence(AI),rationalism and emotionalism have consistently manifested as symptoms of modernity throughout their developmental trajectories.This paper argues that the achievements and crises of both fields signify the triumph of rationalism in the context of deepening modernity,while simultaneously harboring an intrinsic impetus and possibility for transitioning from rationalism to emotionalism.This dynamic serves as a quintessential representation of modernity’s crises and their transcendence.Centered on embodied cognitive science,AI and the metaverse—rooted in rationalism—now face challenges in shifting toward emotionalism,revealing their inadequacy in addressing this shift.Humanity must explore new modernity-deepening paradigms grounded in emotionalism to confront and transcend the potential crises posed by the metaverse and AI.
基金supported by the project of Young Technical Talents of Tianjin Medical University General Hospital(GG-2021-08).
文摘Background:Neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ration(PLR)have been shown to contribute to tumour progression and response to therapy.Methods:We retrospectively counted NLR and PLR in 719 patients with advanced malignancies receiving chemo-and/or immuno-therapy.Results:Both the pretreatment NLR and PLR were significantly elevated in patients with progressive disease than in those without progressive disease.Compared to low groups,the high NLR and PLR groups showed significantly worse event free survival.Conclusion:We propose that NLR and PLR are not only effective blood markers for predicting therapeutic responses to chemo-and/or immuno-therapy,but also useful in detecting survival in diverse malignancies.
基金supported by the Natural Science Foundation of Jiangsu Province(BE2021623,BK20220155)Natural Science Foundation of Jiangsu Province(BE2021623)+4 种基金National Natural Science Foundation of China(32001665,U1903205,32021005)the National Key Research and Development Program of China(2017YF0400303)the Key Scientific and Technological Research Projects in the Key Areas of the Xinjiang Production and Construction Corps(2018AB010)the Key Research and Development 303 Program of Ningxia(2020BFG02012)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.
基金the support from the National Key Research and Development Program of China(No.2023YFA1508500)the National Natural Science Foundation of China(No.22276120)。
文摘Chlorobenzene is a model molecule for researching harmful chlorinated volatile organic compounds.Designing the chemical adsorption site for complex molecules such as chlorobenzene is challenging without a large dataset and reasonable descriptors.Here,the adsorption of chlorobenzene on a phosphorylated CeO_(2)catalyst was analyzed using density functional theory calculations.Three different surface phosphate(H_(x)PO_(4))models were constructed and used to adsorb chlorobenzene.An orbital interaction with fully occupied antibonding is found in one of three physical adsorptions.Based on this,the surface sites of a tri-cluster(M_(3))located at the CeO_(2)surface have been suggested to activate chlorobenzene.Three different clusters have been tested,namely Fe_(3),Ru_(3),and B_(3).All these clusters can activate and twist chlorobenzene by donating electrons.Fe_(3)and Ru_(3)form bonds with weak covalent and strong ionic characters,while B3forms strong covalent bonds between boron and carbon.This work not only predicts a class of sites for chlorobenzene activation that may prevent polychlorinated by-products but also gives a template for catalyst rational design according to fundamental catalytic theory.
