COVID-19 placed increased pressure and urgency for effective cost management,resulting in unprecedented financial strains for hospitals.The pandemic also became a catalyst for accelerating digital transformation to im...COVID-19 placed increased pressure and urgency for effective cost management,resulting in unprecedented financial strains for hospitals.The pandemic also became a catalyst for accelerating digital transformation to improve operations and services in the healthcare industry.Morningdale Hospital is a large and reputable general hospital with a long history in the U.K.You are an intern in the Finance Department of the Hospital.The CEO has asked you to complete a patient-level cost analysis of endoscopic procedures in the Gastrointestinal Department.In your final report,you plan to include a SWOT analysis and a cost analysis using Activity-Based Costing accounting method.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
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
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
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
Lysine methylation is an important post-translational modification that regulates gene transcription,epigenetics,and cell proliferation.Dysregulation of lysine methylation is often observed in cancer cells.Therefore,i...Lysine methylation is an important post-translational modification that regulates gene transcription,epigenetics,and cell proliferation.Dysregulation of lysine methylation is often observed in cancer cells.Therefore,it is important to understand how cells regulate lysine methylation by lysine methyltransferases and lysine demethylases.However,there are still some biologically essential lysine methylation sites without known demethylases,such as H4K20me3 and H3K79me3.Jumonji-C domaincontaining lysine demethylases(JmjC KDMs),as non-heme iron oxygenases,erase methyl marks by hydroxylation of methyl groups,followed by the release of formaldehyde.Current KDM research focuses on the identification of substrates from specific KDMs,but there is a lack of good methods to identify KDM from specific lysine methylation sites.Here,we report a novel strategy to develop activity-based probes that selectively crosslink JmjC-demethylases,which was validated by crosslinking of KDM4A/4D and KDM5B in this study.Allyllysine-containing peptides,as methyllysine substrate mimics,that were prepared by simple cysteine alkylation,are converted to epoxide by demethylase catalysis.The electrophilic intermediate subsequently crosslinks residues inside the KDM catalytic pocket.Therefore,such probes that selectively conjugate KDMs could be applied to identify KDMs from specific methyllysine sites and uncover new biology of lysine methylation.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
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
Ubiquitin-propargylamide(Ub-PA) is one of the most widely used activity-based probe to measure the activity of deubiquitinases(DUBs) and help validate DUBs targeting inhibitors. However, current synthetic route of Ub-...Ubiquitin-propargylamide(Ub-PA) is one of the most widely used activity-based probe to measure the activity of deubiquitinases(DUBs) and help validate DUBs targeting inhibitors. However, current synthetic route of Ub-PA is cumbersome. In this work, we report a novel semi-synthetic strategy to prepare Ub-PA in large-scale. Biochemical assays prove that semi-synthetic Ub-PA is an effective probe in identifying DUBs targeting inhibitors.展开更多
Wortmannin, a known inhibitor of phosphoinositide 3-kinases(PI3 Ks), their low selectivity and high toxicity is still problematic and less is known about their effects on PI3 Ks in cellular systems. Hence, we have syn...Wortmannin, a known inhibitor of phosphoinositide 3-kinases(PI3 Ks), their low selectivity and high toxicity is still problematic and less is known about their effects on PI3 Ks in cellular systems. Hence, we have synthesized a series of multifunctional wortmannin probes with the ability to self-activate, by installing a clickable handle at C11 site, and secondary amine and cancer-targeting moiety at C20 site respectively. MTT assay first confirmed that self-activating probes have better inhibition potency and biotin enhanced their cancer cell uptake. Further experiments showed most of probes can target PI3 K/Akt/mTOR pathway with prolonged turn-over time. Protein profiling and pull-down results were observed that the derivatives not only labelled four PI3 Ks with selectivity, but also engaged in covalent interactions with numerous cellular proteins which could be the major reason of their high toxicity.展开更多
文摘COVID-19 placed increased pressure and urgency for effective cost management,resulting in unprecedented financial strains for hospitals.The pandemic also became a catalyst for accelerating digital transformation to improve operations and services in the healthcare industry.Morningdale Hospital is a large and reputable general hospital with a long history in the U.K.You are an intern in the Finance Department of the Hospital.The CEO has asked you to complete a patient-level cost analysis of endoscopic procedures in the Gastrointestinal Department.In your final report,you plan to include a SWOT analysis and a cost analysis using Activity-Based Costing accounting method.
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 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 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(22422703)the Zhejiang Provincial Natural Science Foundation of China(XHD23B0701)the Westlake University Startup。
文摘Lysine methylation is an important post-translational modification that regulates gene transcription,epigenetics,and cell proliferation.Dysregulation of lysine methylation is often observed in cancer cells.Therefore,it is important to understand how cells regulate lysine methylation by lysine methyltransferases and lysine demethylases.However,there are still some biologically essential lysine methylation sites without known demethylases,such as H4K20me3 and H3K79me3.Jumonji-C domaincontaining lysine demethylases(JmjC KDMs),as non-heme iron oxygenases,erase methyl marks by hydroxylation of methyl groups,followed by the release of formaldehyde.Current KDM research focuses on the identification of substrates from specific KDMs,but there is a lack of good methods to identify KDM from specific lysine methylation sites.Here,we report a novel strategy to develop activity-based probes that selectively crosslink JmjC-demethylases,which was validated by crosslinking of KDM4A/4D and KDM5B in this study.Allyllysine-containing peptides,as methyllysine substrate mimics,that were prepared by simple cysteine alkylation,are converted to epoxide by demethylase catalysis.The electrophilic intermediate subsequently crosslinks residues inside the KDM catalytic pocket.Therefore,such probes that selectively conjugate KDMs could be applied to identify KDMs from specific methyllysine sites and uncover new biology of lysine methylation.
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.
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.
基金supported by the National Natural Science Foundation of China(Nos. 91753205 and 21877024 to Y. Li and No. 31640016 to Z. Mei)the Fundamental Research Funds for the Central Universities (No. PA2017GDQT0021 to Y. Li)+2 种基金the funding of National Key R&D program of China(No. 2017YFD0500400 to Z. Mei)the Fundamental Research Funds for the Central Non-profit Scientific Institution (No. Y2016JC25 to Z. Mei)the Agricultural Science and Technology Innovation Program to Z.Mei
文摘Ubiquitin-propargylamide(Ub-PA) is one of the most widely used activity-based probe to measure the activity of deubiquitinases(DUBs) and help validate DUBs targeting inhibitors. However, current synthetic route of Ub-PA is cumbersome. In this work, we report a novel semi-synthetic strategy to prepare Ub-PA in large-scale. Biochemical assays prove that semi-synthetic Ub-PA is an effective probe in identifying DUBs targeting inhibitors.
基金financially supported by the Natural Science Foundation of Zhejiang Province (Nos. LQ16B020003, LY17B060009)the National Natural Science Foundation of China (Nos. 21708034, 21472172, 81672508, 61505076)Jiangsu Provincial Foundation for Distinguished Young Scholars (No. BK20170041)
文摘Wortmannin, a known inhibitor of phosphoinositide 3-kinases(PI3 Ks), their low selectivity and high toxicity is still problematic and less is known about their effects on PI3 Ks in cellular systems. Hence, we have synthesized a series of multifunctional wortmannin probes with the ability to self-activate, by installing a clickable handle at C11 site, and secondary amine and cancer-targeting moiety at C20 site respectively. MTT assay first confirmed that self-activating probes have better inhibition potency and biotin enhanced their cancer cell uptake. Further experiments showed most of probes can target PI3 K/Akt/mTOR pathway with prolonged turn-over time. Protein profiling and pull-down results were observed that the derivatives not only labelled four PI3 Ks with selectivity, but also engaged in covalent interactions with numerous cellular proteins which could be the major reason of their high toxicity.
