Traumatic injuries to spinal cord elicit diverse signaling pathways leading to unselective and complex pathological outcomes:death of multiple classes of neural cells,formation of cystic cavities and glial scars,disr...Traumatic injuries to spinal cord elicit diverse signaling pathways leading to unselective and complex pathological outcomes:death of multiple classes of neural cells,formation of cystic cavities and glial scars,disruption of axonal connections,and demyelination of spared axons,all of which can contribute more or less to debilitating functional impairments found in patients with spinal cord injury.展开更多
To analyse and optimize a enterprise process in a wide scope, an activity-based method of modeling resource capabilities is presented. It models resource capabilities by means of the same structure as an activity, tha...To analyse and optimize a enterprise process in a wide scope, an activity-based method of modeling resource capabilities is presented. It models resource capabilities by means of the same structure as an activity, that is, resource capabilities are defined by input objects, actions and output objects. A set of activity-based resource capability modeling hales and matching rules between an activity and a resource are introduced. This method can not only be used to describe capability of manufacturing tools, but also capability of persons and applications, etc. It unifies methods of modeling capability of all kinds of resources in an enterprise and supports the ootimization of the resource allocation of a orocess.展开更多
Implementing effective cost management approaches has recently gained momentum due to intense competition and increasing customer demands. Moreover, effective cost management approaches have contributed to firms' com...Implementing effective cost management approaches has recently gained momentum due to intense competition and increasing customer demands. Moreover, effective cost management approaches have contributed to firms' competitive advantage in relation to cost leadership strategy. Consequently, firms have implemented contemporary cost management systems, such as activity-based management, business process re-engineering, life-cycle costing, target costing, and theory of constraint (TOC), to enable them to become low-cost producers and compete effectively and sustain their performance. Furthermore, focusing on cost management to improve profitability has led to the integration of activity-based costing (ABC) and TOC. Therefore, the aim of this study is to review literature and discuss how integration of ABC and TOC can result in improved and sustained cost management. While these methods have different approaches in addressing cost management, treating them as complementary cost management approaches can result in improved cost management due to improved product costing, improved cost reporting, improved product-mix decisions, and improved cycle-time management. Improvement in cost management will then result in sustained cost management. Sustained cost management is further enhanced with the investment in information customer and shareholder value technology that supports cross-functional decision making to continue creating to remain competitive in the market.展开更多
In order to evaluate and estimate me cosEs oi prouuct~ plt, uu^u e vironment properly, an improved activity-based costing (ABC) model is presented. By utilizing the input-output analysis method, the complex consumpt...In order to evaluate and estimate me cosEs oi prouuct~ plt, uu^u e vironment properly, an improved activity-based costing (ABC) model is presented. By utilizing the input-output analysis method, the complex consumption relationships in a complex manufacturing environment are first expressed. The consumption characteristics (mainly presented by the activity rates) of all production activities are extracted by solving these relationships. Then with the con- sumption characteristics and operating parameters of these activities, the detailed cost consumption of a product in its manufacturing process is estimated. A case study is finally given based on the compressor products of a manufacturing company, and its effectiveness is shown. As the cost influ- ence of complex consumption relationships is fully considered, the limitation of traditional ABC method is overcome, and therefore a high accuracy in product cost estimation under the complex manufacturing environment can be achieved.展开更多
An organization’s costing system is a system that helps the management with the strategy planning while the system plays an important role in providing accurate cost information about the products and customers.In ot...An organization’s costing system is a system that helps the management with the strategy planning while the system plays an important role in providing accurate cost information about the products and customers.In other words,the costing management system is important to provide timely and quality information to help managers in their decision-making process.Producing quality graduates is the main objective of any university and the cost of quality or the cost of poor quality is one that is often difficult to measure in higher education.This can be partly attributed to the fact that most accounting systems are not structured to capture important cost-of-quality information.In order to succeed,many organizations tend to shift from conventional or traditional costing system to Activity-based costing(ABC).ABC provides both higher education administrators and policymakers with better information on which to base decisions.The use of multiple cost pools and drivers under ABC leads to more detailed and accurate product costing than that provided by traditional cost systems.This paper attempts to investigate the possibilities and limitations of implementing ABC in universities.More specifically the study makes use of the case study method to illustrate the implementation of activity-based costing of library services in a private university in the Kingdom of Bahrain.The research methodology of the case study is a combination of both descriptive and quantitative analyses.The study identified six categories of cost pools which are related to the activities of the library as well as 17 relevant cost drivers.Accordingly,ABC should lead to a better understanding of what drives costs and,by extension,what changes are necessary to reduce costs.Unnecessary activities that do not add value to services can be identified and eliminated.Further ABC is feasible in an academic library and that much can be gained from the process of analyzing activities.However,more work needs to be done in terms of designing accounting and other information systems to capture cost and activity transaction data in a more routine and disaggregated form for ABC analysis.展开更多
Based on the theory of activity-based costing and the idea of value chain,activity optimization and cost control are carried out on the whole construction process of agricultural water conservancy projects. Through th...Based on the theory of activity-based costing and the idea of value chain,activity optimization and cost control are carried out on the whole construction process of agricultural water conservancy projects. Through the use of literature review,case analysis and statistical analysis and other methods,with agricultural water conservancy projects as the research object,and comparing activity-based costing with the traditional model of cost accounting,the writer carries out the corresponding value chain analysis,and comes to the following conclusion: the statistical calculation and analysis of the entire construction process based on activity-based costing can accurately and effectively control the costs of water conservancy projects. Through the use of activity-based costing,the cost data of agricultural water conservancy projects is more detailed and accurate,and cost management personnel can also find non-value-added activities,optimize the enterprise's value chain and achieve cost control objectives through the analysis of the activity chain and value chain of agricultural water conservancy projects.展开更多
Road transport is a flexible mode of transport and its importance in era of globalization increases. Management of road transport companies is, in this turbulent environment, exposed to many technical, legislative, an...Road transport is a flexible mode of transport and its importance in era of globalization increases. Management of road transport companies is, in this turbulent environment, exposed to many technical, legislative, and economic problems. Especially, the growing economic pressure leads to an urgent requirement of the manager and control system improvement. Activity-based costing (ABC) method is a very powerful tool to improve products, services, processes, and market strategies. ABC allows company management to understand what causes costs and how to manage them. Company under this scheme may get a glimpse of how efficiently a company converts the source value. The main objective of our research was to assess the possibility of application of the ABC method in a transport undertaking. ABC method as a fundamentally different view on the cost in the transport business helps to find the reasons of cost and thereby influences their levels to make better use of resources.. New managerial accounting methods aim to show management what information is needed, how and where this information can be obtained, and how they can be useful for the management of the company's proper planning, decision-making, and control. Information provided by management accounting is often a key factor in the analysis of alternative ways of solving problems. This article focuses on the transport enterprise management and helps to decide on the use of this method in business practice.展开更多
Protein S-sulfenylation(protein sulfenic acid),as one of the most significant oxidative post-translational modifications(OxiPTMs),plays a vital role in regulating protein function.A variety of activity-based probes ha...Protein S-sulfenylation(protein sulfenic acid),as one of the most significant oxidative post-translational modifications(OxiPTMs),plays a vital role in regulating protein function.A variety of activity-based probes have been developed to profile sulfenic acid in living cells.However,due to the transient presence and low content of sulfenic acid in living cell,high doses of probes are needed to achieve efficient labeling.More importantly,current probes have no temporal control over sulfenic acid labeling.To overcome these limitations,two caged cysteine sulfenic acid probes DYn-2-ONB and DYn-2-Cou with either an o-nitrobenzyl or coumarin protecting group were developed in this study.Both probes can be efficiently uncaged via irradiation to produce the active C-nucleophile probe DYn-2.Labeling assay in living cells demonstrated DYn-2-ONB exhibited better labeling capacity compared with DYn-2,providing it as a powerful tool for improved monitoring of protein S-sulfenylation in living cells.展开更多
Activity-based Ubiquitin probes(Ub-ABPs)carrying a reporter group have emerged as effective tools for the investigation of deubiquitinating enzymes(DUBs),such as studying the molecular mechanism of DUBs,profiling new ...Activity-based Ubiquitin probes(Ub-ABPs)carrying a reporter group have emerged as effective tools for the investigation of deubiquitinating enzymes(DUBs),such as studying the molecular mechanism of DUBs,profiling new DUBs.But so far,the synthesis of commonly used biotin-bearing Ub-ABPs is a technical challenge.Here,we report a one-pot semi-synthetic strategy for the acquiring of Ub-ABPs carrying a biotin tag through sequential enzymatic ligation,N-S acyl transfer and aminolysis reaction without any purification steps.These probes enable to capture the different family of DUBs for enrichment and immunoblotting using the attached biotin tag.展开更多
Formaldehyde(FA)plays critical roles in Alzheimer's disease and the associations between FA and Alzheimer's disease(AD)are still obscure.To reveal FA fluxes in the Alzheimer's disease brain,an activity-bas...Formaldehyde(FA)plays critical roles in Alzheimer's disease and the associations between FA and Alzheimer's disease(AD)are still obscure.To reveal FA fluxes in the Alzheimer's disease brain,an activity-based fluorescence probe NP-FA with superb blood-brain barrier permeable abilities was exquisitely designed.The probe responded to FA with significant fluorescence increases(F/F0=81),thus laying the foundation for the sensitive detection of FA in cuvette and in vivo.Moreover,the probe also possessed some fasci-nating performances,including endoplasmic reticulum(ER)-targeting abilities,good one-photon/two-photon absorption properties,and appropriate hydrophobicity property(log P=2.34±0.05).As a result,the probe can readily reflect the overproduction of FA con-tent in live cells under ER stress by high-fidelity two-photon imaging.More interestingly,ex vivo imaging of AD brains and two-photon imaging of AD slice tissues visually disclosed that the FA level of AD brain is much higher than that of the normal brain.This work afforded a specific activity-based probe for the imaging of FA in the AD mouse brains,which could be further extended to FA-related studies in Alzheimer's disease.展开更多
Activity-based approaches for designing AIEgens possess prominent advantages including high selectivity,sensitivity,and signal-to-noise ratio,and they have received more attention in recent years.Excellent activatable...Activity-based approaches for designing AIEgens possess prominent advantages including high selectivity,sensitivity,and signal-to-noise ratio,and they have received more attention in recent years.Excellent activatable AIE probes have been reported for detecting toxic substances,imaging intracellular active molecules/biomolecules,as well as monitoring the activity of overexpressed enzymes in cancers.Moreover,the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation,while they have no distinct effect on normal cells,demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy.Thus,in this review,we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications.The challenges of activatable AIE probes and the corresponding solutions are described.We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.展开更多
Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of cela...Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.展开更多
Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an i...Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.展开更多
This paper is an exploratory study which investigates the introduction and implementation of management accounting changes in Australia. The study first examines the introduction of relatively new management accountin...This paper is an exploratory study which investigates the introduction and implementation of management accounting changes in Australia. The study first examines the introduction of relatively new management accounting techniques in professional journals, conferences, workshops, and professional development programs over a four-year period in Australia. These are among the main sources of transferring information on cost and management accounting changes to potential users in Australia. The purpose of such a study is to get a clear picture of the scope and extent of recently developed cost and management accounting techniques introduced to practitioners in Australia. By identifying the major management accounting changes and developments faced by organizations, the study then investigates the extent of implementations of such changes in practice. The study further explores the hindering and facilitating factors contributing to the implementation of new management accounting changes in organizations.展开更多
Most drugs exert pharmacological effects through interaction with their target proteins.Therefore,drug target identification is a crucial step towards the understanding of the mechanism of drug action.It is also imper...Most drugs exert pharmacological effects through interaction with their target proteins.Therefore,drug target identification is a crucial step towards the understanding of the mechanism of drug action.It is also imperative to study the pharmacodynamics of a known drug,with an aim to discover the potentially unrevealed actions and thus refine its future clinical applications.Currently,drug-target identification is either through in vitro affinity chromatography-based approaches or in vivo activity-based protein profiling(ABPP)approaches.However,these approaches generally face difficulties discriminating specific drug targets from non-specific ones.To address this issue,we have come up with a strategy by coupling iTRAQTM(isobaric tags for relative and absolute quantitation)quantitative proteomics approach with clickable ABPP,to specifically and compre hensively identify drug targets in live cells.Using this approach,we identified the protein targets of andrographolide,a natural product with known anti-inflammation and anti-cancer effects,in live cancer cells.The identified target list not only confirmed the known functions of the drug but also revealed its potential novel application as a tumor metastasis inhibitor.We have also used this strategy,combining with a cleavable probe to identify the protein targets of aspirin and its binding sites.Our results revealed the roles of aspirin ininhibition of protein synthesis and induction of autophagy,which have been functionally validated.Our strategy is widely applicable to the identification of protein targets of covalent drugs.展开更多
This paper firstly introduced theoretical background of the Activity-Based Costing(ABC). Then,it analyzed necessity,extension resistance and difficulty of ABC approach in agri-scientific research institutions. Finally...This paper firstly introduced theoretical background of the Activity-Based Costing(ABC). Then,it analyzed necessity,extension resistance and difficulty of ABC approach in agri-scientific research institutions. Finally,it came up with some recommendations for scientifically learning and steadily promoting ABC method in agri-scientific research field.展开更多
This paper aims to examine the role and significance of activity-based budgeting(ABB)in developing countries.It provides comparison with the traditional system,and evaluates the possibility of implementing ABB system ...This paper aims to examine the role and significance of activity-based budgeting(ABB)in developing countries.It provides comparison with the traditional system,and evaluates the possibility of implementing ABB system in private Libyan commercial companies(PLCC).This paper attempts to highlight the factors affecting the implementation of ABB in PLCC.The findings suggest that PLCC still uses traditional system in budget preparation.展开更多
In the implementation of activity-based costing, cost driver is the true reason to determine the occurrence of costs and the consumption of resources, and correctly selecting the cost driver is the key to calculating ...In the implementation of activity-based costing, cost driver is the true reason to determine the occurrence of costs and the consumption of resources, and correctly selecting the cost driver is the key to calculating the cost of the product accurately. Beginning with the meaning of cost driver and its characteristics, this article analyses its classification, and then, focuses on its selection method.展开更多
基金supported by a National Research Foundation of Korea grant funded by the Korean Government(NRF-2014R1A1A2056452 to D.H.H.and NRF-2014M3A9B6034224 to BGK)
文摘Traumatic injuries to spinal cord elicit diverse signaling pathways leading to unselective and complex pathological outcomes:death of multiple classes of neural cells,formation of cystic cavities and glial scars,disruption of axonal connections,and demyelination of spared axons,all of which can contribute more or less to debilitating functional impairments found in patients with spinal cord injury.
基金the Natural High-Technology Development Program for CIMS of China(Grant No.2003AA413210)
文摘To analyse and optimize a enterprise process in a wide scope, an activity-based method of modeling resource capabilities is presented. It models resource capabilities by means of the same structure as an activity, that is, resource capabilities are defined by input objects, actions and output objects. A set of activity-based resource capability modeling hales and matching rules between an activity and a resource are introduced. This method can not only be used to describe capability of manufacturing tools, but also capability of persons and applications, etc. It unifies methods of modeling capability of all kinds of resources in an enterprise and supports the ootimization of the resource allocation of a orocess.
文摘Implementing effective cost management approaches has recently gained momentum due to intense competition and increasing customer demands. Moreover, effective cost management approaches have contributed to firms' competitive advantage in relation to cost leadership strategy. Consequently, firms have implemented contemporary cost management systems, such as activity-based management, business process re-engineering, life-cycle costing, target costing, and theory of constraint (TOC), to enable them to become low-cost producers and compete effectively and sustain their performance. Furthermore, focusing on cost management to improve profitability has led to the integration of activity-based costing (ABC) and TOC. Therefore, the aim of this study is to review literature and discuss how integration of ABC and TOC can result in improved and sustained cost management. While these methods have different approaches in addressing cost management, treating them as complementary cost management approaches can result in improved cost management due to improved product costing, improved cost reporting, improved product-mix decisions, and improved cycle-time management. Improvement in cost management will then result in sustained cost management. Sustained cost management is further enhanced with the investment in information customer and shareholder value technology that supports cross-functional decision making to continue creating to remain competitive in the market.
基金Supported by the National Natural Science Foundation of China(No.61074136)the National Science and Technology Major Project of China(No.2009ZX04014)
文摘In order to evaluate and estimate me cosEs oi prouuct~ plt, uu^u e vironment properly, an improved activity-based costing (ABC) model is presented. By utilizing the input-output analysis method, the complex consumption relationships in a complex manufacturing environment are first expressed. The consumption characteristics (mainly presented by the activity rates) of all production activities are extracted by solving these relationships. Then with the con- sumption characteristics and operating parameters of these activities, the detailed cost consumption of a product in its manufacturing process is estimated. A case study is finally given based on the compressor products of a manufacturing company, and its effectiveness is shown. As the cost influ- ence of complex consumption relationships is fully considered, the limitation of traditional ABC method is overcome, and therefore a high accuracy in product cost estimation under the complex manufacturing environment can be achieved.
文摘An organization’s costing system is a system that helps the management with the strategy planning while the system plays an important role in providing accurate cost information about the products and customers.In other words,the costing management system is important to provide timely and quality information to help managers in their decision-making process.Producing quality graduates is the main objective of any university and the cost of quality or the cost of poor quality is one that is often difficult to measure in higher education.This can be partly attributed to the fact that most accounting systems are not structured to capture important cost-of-quality information.In order to succeed,many organizations tend to shift from conventional or traditional costing system to Activity-based costing(ABC).ABC provides both higher education administrators and policymakers with better information on which to base decisions.The use of multiple cost pools and drivers under ABC leads to more detailed and accurate product costing than that provided by traditional cost systems.This paper attempts to investigate the possibilities and limitations of implementing ABC in universities.More specifically the study makes use of the case study method to illustrate the implementation of activity-based costing of library services in a private university in the Kingdom of Bahrain.The research methodology of the case study is a combination of both descriptive and quantitative analyses.The study identified six categories of cost pools which are related to the activities of the library as well as 17 relevant cost drivers.Accordingly,ABC should lead to a better understanding of what drives costs and,by extension,what changes are necessary to reduce costs.Unnecessary activities that do not add value to services can be identified and eliminated.Further ABC is feasible in an academic library and that much can be gained from the process of analyzing activities.However,more work needs to be done in terms of designing accounting and other information systems to capture cost and activity transaction data in a more routine and disaggregated form for ABC analysis.
文摘Based on the theory of activity-based costing and the idea of value chain,activity optimization and cost control are carried out on the whole construction process of agricultural water conservancy projects. Through the use of literature review,case analysis and statistical analysis and other methods,with agricultural water conservancy projects as the research object,and comparing activity-based costing with the traditional model of cost accounting,the writer carries out the corresponding value chain analysis,and comes to the following conclusion: the statistical calculation and analysis of the entire construction process based on activity-based costing can accurately and effectively control the costs of water conservancy projects. Through the use of activity-based costing,the cost data of agricultural water conservancy projects is more detailed and accurate,and cost management personnel can also find non-value-added activities,optimize the enterprise's value chain and achieve cost control objectives through the analysis of the activity chain and value chain of agricultural water conservancy projects.
文摘Road transport is a flexible mode of transport and its importance in era of globalization increases. Management of road transport companies is, in this turbulent environment, exposed to many technical, legislative, and economic problems. Especially, the growing economic pressure leads to an urgent requirement of the manager and control system improvement. Activity-based costing (ABC) method is a very powerful tool to improve products, services, processes, and market strategies. ABC allows company management to understand what causes costs and how to manage them. Company under this scheme may get a glimpse of how efficiently a company converts the source value. The main objective of our research was to assess the possibility of application of the ABC method in a transport undertaking. ABC method as a fundamentally different view on the cost in the transport business helps to find the reasons of cost and thereby influences their levels to make better use of resources.. New managerial accounting methods aim to show management what information is needed, how and where this information can be obtained, and how they can be useful for the management of the company's proper planning, decision-making, and control. Information provided by management accounting is often a key factor in the analysis of alternative ways of solving problems. This article focuses on the transport enterprise management and helps to decide on the use of this method in business practice.
基金supported by the National Natural Science Foundation of China(Nos.31871365 and 22177029)Fundamental Research Funds for the Central Universities.
文摘Protein S-sulfenylation(protein sulfenic acid),as one of the most significant oxidative post-translational modifications(OxiPTMs),plays a vital role in regulating protein function.A variety of activity-based probes have been developed to profile sulfenic acid in living cells.However,due to the transient presence and low content of sulfenic acid in living cell,high doses of probes are needed to achieve efficient labeling.More importantly,current probes have no temporal control over sulfenic acid labeling.To overcome these limitations,two caged cysteine sulfenic acid probes DYn-2-ONB and DYn-2-Cou with either an o-nitrobenzyl or coumarin protecting group were developed in this study.Both probes can be efficiently uncaged via irradiation to produce the active C-nucleophile probe DYn-2.Labeling assay in living cells demonstrated DYn-2-ONB exhibited better labeling capacity compared with DYn-2,providing it as a powerful tool for improved monitoring of protein S-sulfenylation in living cells.
基金supported by the National Key R&D Program of China(No.2017YFA0505400)the National Natural Science Foundation of China(Nos.21877024,21972214 and 22277020)。
文摘Activity-based Ubiquitin probes(Ub-ABPs)carrying a reporter group have emerged as effective tools for the investigation of deubiquitinating enzymes(DUBs),such as studying the molecular mechanism of DUBs,profiling new DUBs.But so far,the synthesis of commonly used biotin-bearing Ub-ABPs is a technical challenge.Here,we report a one-pot semi-synthetic strategy for the acquiring of Ub-ABPs carrying a biotin tag through sequential enzymatic ligation,N-S acyl transfer and aminolysis reaction without any purification steps.These probes enable to capture the different family of DUBs for enrichment and immunoblotting using the attached biotin tag.
基金the National Natural Science Foundation of China(Nos.22174034,21804033,and 21625503)the Natural Science Foundation of Hubei Province(2021CFB305)。
文摘Formaldehyde(FA)plays critical roles in Alzheimer's disease and the associations between FA and Alzheimer's disease(AD)are still obscure.To reveal FA fluxes in the Alzheimer's disease brain,an activity-based fluorescence probe NP-FA with superb blood-brain barrier permeable abilities was exquisitely designed.The probe responded to FA with significant fluorescence increases(F/F0=81),thus laying the foundation for the sensitive detection of FA in cuvette and in vivo.Moreover,the probe also possessed some fasci-nating performances,including endoplasmic reticulum(ER)-targeting abilities,good one-photon/two-photon absorption properties,and appropriate hydrophobicity property(log P=2.34±0.05).As a result,the probe can readily reflect the overproduction of FA con-tent in live cells under ER stress by high-fidelity two-photon imaging.More interestingly,ex vivo imaging of AD brains and two-photon imaging of AD slice tissues visually disclosed that the FA level of AD brain is much higher than that of the normal brain.This work afforded a specific activity-based probe for the imaging of FA in the AD mouse brains,which could be further extended to FA-related studies in Alzheimer's disease.
基金National Research Foundation of Korea,Grant/Award Number:2012R1A3A2048814National Natural Science Foundation of China,Grant/Award Number:22090011。
文摘Activity-based approaches for designing AIEgens possess prominent advantages including high selectivity,sensitivity,and signal-to-noise ratio,and they have received more attention in recent years.Excellent activatable AIE probes have been reported for detecting toxic substances,imaging intracellular active molecules/biomolecules,as well as monitoring the activity of overexpressed enzymes in cancers.Moreover,the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation,while they have no distinct effect on normal cells,demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy.Thus,in this review,we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications.The challenges of activatable AIE probes and the corresponding solutions are described.We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.
基金the National Key Research and Development Program of China(2020YFA0908000,2022YFC2303600)the National Natural Science Foundation of China(81903866,82274182)and the Central Public Welfare Research Institutes(ZZ13-YQ-105,ZZ15-YQ-065,ZZ14-YQ-058).
文摘Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.
基金suppor ted by the National Key Research and Development Program of China(2020YFA0908000)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)+2 种基金the National Natural Science Foundation of China(82074098,82003814)the CACMS Innovation Fund(CI2021A05101)the Fundamental Research Funds for the Central public welfare research institutes(ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-ND-010,ZZ15-ND-10 and ZZ14-FL-002)。
文摘Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.
文摘This paper is an exploratory study which investigates the introduction and implementation of management accounting changes in Australia. The study first examines the introduction of relatively new management accounting techniques in professional journals, conferences, workshops, and professional development programs over a four-year period in Australia. These are among the main sources of transferring information on cost and management accounting changes to potential users in Australia. The purpose of such a study is to get a clear picture of the scope and extent of recently developed cost and management accounting techniques introduced to practitioners in Australia. By identifying the major management accounting changes and developments faced by organizations, the study then investigates the extent of implementations of such changes in practice. The study further explores the hindering and facilitating factors contributing to the implementation of new management accounting changes in organizations.
文摘Most drugs exert pharmacological effects through interaction with their target proteins.Therefore,drug target identification is a crucial step towards the understanding of the mechanism of drug action.It is also imperative to study the pharmacodynamics of a known drug,with an aim to discover the potentially unrevealed actions and thus refine its future clinical applications.Currently,drug-target identification is either through in vitro affinity chromatography-based approaches or in vivo activity-based protein profiling(ABPP)approaches.However,these approaches generally face difficulties discriminating specific drug targets from non-specific ones.To address this issue,we have come up with a strategy by coupling iTRAQTM(isobaric tags for relative and absolute quantitation)quantitative proteomics approach with clickable ABPP,to specifically and compre hensively identify drug targets in live cells.Using this approach,we identified the protein targets of andrographolide,a natural product with known anti-inflammation and anti-cancer effects,in live cancer cells.The identified target list not only confirmed the known functions of the drug but also revealed its potential novel application as a tumor metastasis inhibitor.We have also used this strategy,combining with a cleavable probe to identify the protein targets of aspirin and its binding sites.Our results revealed the roles of aspirin ininhibition of protein synthesis and induction of autophagy,which have been functionally validated.Our strategy is widely applicable to the identification of protein targets of covalent drugs.
基金Supported by Project of Hubei Provincial Soft Science Research Plan(2011DEA023)
文摘This paper firstly introduced theoretical background of the Activity-Based Costing(ABC). Then,it analyzed necessity,extension resistance and difficulty of ABC approach in agri-scientific research institutions. Finally,it came up with some recommendations for scientifically learning and steadily promoting ABC method in agri-scientific research field.
文摘This paper aims to examine the role and significance of activity-based budgeting(ABB)in developing countries.It provides comparison with the traditional system,and evaluates the possibility of implementing ABB system in private Libyan commercial companies(PLCC).This paper attempts to highlight the factors affecting the implementation of ABB in PLCC.The findings suggest that PLCC still uses traditional system in budget preparation.
文摘In the implementation of activity-based costing, cost driver is the true reason to determine the occurrence of costs and the consumption of resources, and correctly selecting the cost driver is the key to calculating the cost of the product accurately. Beginning with the meaning of cost driver and its characteristics, this article analyses its classification, and then, focuses on its selection method.