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
Peroxynitrite(ONOO^(-))contributes to oxidative stress and neurodegeneration in Parkinson's disease(PD).Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO^(-)flux and unde...Peroxynitrite(ONOO^(-))contributes to oxidative stress and neurodegeneration in Parkinson's disease(PD).Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO^(-)flux and understanding of the ONOO^(-)stress-induced neuropathology of PD.Herein,a novelα-ketoamide-based fluorogenic probe(DFlu)was designed for ONOO^(-)monitoring in multiple PD models.The results demonstrated that DFlu exhibits a fluorescence turn-on response to ONOO^(-)with high specificity and sensitivity.The efficacy of DFlu for intracellular ONOO^(-)imaging was demonstrated systematically.The results showed that DFlu can successfully visualize endogenous and exogenous ONOO^(-)in cells derived from chemical and biochemical routes.More importantly,the two-photon excitation ability of DFlu has been well demonstrated by monitoring exogenous/endogenous ONOO^(-)production and scavenging in live zebraflsh PD models.This work provides a reliable and promisingα-ketoamide-based optical tool for identifying variations of ONOO^(-)in PD models.展开更多
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
The research presented in this paper aimed to analyze the evolution of fractures in strata in relation to the progress of longwall mining.To achieve this objective,an introscopic probe equipped with a highresolution c...The research presented in this paper aimed to analyze the evolution of fractures in strata in relation to the progress of longwall mining.To achieve this objective,an introscopic probe equipped with a highresolution camera was developed,along with additional equipment that enables continuous recording of the internal surfaces of drainage boreholes exceeding 100 m in depth.The probe was utilized to test two methane drainage boreholes in the Z-3b longwall,which operates within the 501/3 coal seam of the Jankowice mine in Poland.Automatic image analysis methods were applied to evaluate the recorded images,based on a newly developed classificationsystem for fractures categorized by size and number.The results were compared with an analysis of changes in the methane capture rate from the drainage boreholes,which correlated with longwall mining progress.A strong correlation was observed between the number of fractures and the lithology of the strata layers.The largest number of fractures and their evolution were recorded in the coal layers,followed by the shale layers,while the sandstone layers exhibited the least number of fractures.Based on parallel measurements of the methane capture rate from the drainage boreholes during the progress of longwall mining,the extent of the strata's fracture zone was determined to range from 6 m to 36 m.Within the fracture zone,the strata are highly fractured,which leads to an increase in methane emissions through seepage and diffusion processes.展开更多
Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogen...Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogenous antioxidants,have been proposed as potential biomarkers for the disease.However,due to the presence of the blood-brain barrier(BBB),fluorescent probes are rarely used to image biothiols in the brain of SCZ models.In this study,a series of fluorescent probes for biothiols were developed using dicyanoisophorone derivatives as fluorophores known for their excellent optical properties,and carboxylic esters as recognition units.A parallel synthesis and rapid screening strategy was employed to construct and optimize these probes.By introducing trifluoromethyl and benzothiazole groups into the fluorophore,the emission wavelength was successfully shifted into the near-infrared region.Additionally,various trifluoromethyl-substituted aromatic and nitrogen heterocyclic compounds were incorporated to optimize the carboxylic esters,thereby improving the probes' reactivity and lipophilicity.Systematic evaluation of the physicochemical characteristics,and optical performance led to the identification of DCIBT-11 as the most promising candidate.DCI-BT-11 demonstrated excellent BBB permeability and a good response to biothiols both in vitro and in vivo.Notably,DCI-BT-11 was used for the first time to visualize biothiol flux and assess the therapeutic effects of the antioxidant N-acetylcysteine(NAC) in the brains of SCZ mouse models,offering new insights into the role of OS in the pathogenesis and treatment of SCZ.展开更多
Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of...Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of multiple RSSs significant for evaluating ferroptosis therapy.However,the traditional techniques,including fluorescent(FL) imaging and electrospray ionization-based mass spectrometry(MS) detection,cannot achieve the discrimination of different RSSs.Herein,simultaneous MS detection of multiple RSSs,including cysteine(Cys),homocysteine(Hcy),glutathione(GSH) and hydrogen sulfide(H_(2)S),was obtained upon enhancing ionization efficiency by a fluorescent probe(NBD-O-1).Based on the interaction between NBD-O-1 and RSSs,the complex of RSSs with a fragment of NBD-O-1 can be generated,which can be easily ionized for MS detection in the negative mode.Therefore,the intracellular RSSs can be well detected upon the incubation of He La cells with the probe of NBD-O-1,exhibiting the total RSS levels by the FL imaging and further providing expression of each RSS by enhanced MS detection.Furthermore,the RSSs during ferroptosis in He La cells have been evaluated using the present strategy,demonstrating the potential for ferroptosis examinations.This work has made an unconventional application of a fluorescent probe to enhance the detection of multiple RSSs by MS,providing significant molecular information for addressing the ferroptosis mechanism.展开更多
Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
The thoracic duct(TD),the largest lymphatic vessel in the human body,plays a critical role in returning lymph to the circulatory system.However,its dynamic,distensible nature and concealed anatomical location make int...The thoracic duct(TD),the largest lymphatic vessel in the human body,plays a critical role in returning lymph to the circulatory system.However,its dynamic,distensible nature and concealed anatomical location make intraoperative visualization critically challenging and increase the risk of injury.Real-time,high-resolution assessment of TD leaks remains an urgent clinical need.Here,we present a breakthrough molecular engineering strategy that leverages an intestinally lipophilic fluorescent formulation for dynamic in vivo TD imaging.Our rationally designed cyanine derivative IR790+,known for its rapid membrane permeability and endoplasmic reticulum(ER)targeting localization,demonstrates unprecedented chylomicron affinity,which subsequently transports the dye through the lymphatic system to the TD.Notably,dynamic,high-contrast intraoperative TD imaging is achieved from rat models to swine models.Administered orally as near-infrared(NIR)fluorescent contrast agent,this ultra-stable IR790+@oil formulation,engineered via flash nanoprecipitation,surpasses conventional counterparts by enabling non-invasive,real-time identification of TD.Intriguingly,this first-reported ER-targeting NIR formulation,delivered orally,represents a paradigm shift in fluorescence-guided surgery,significantly improving intraoperative accuracy.展开更多
The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensit...The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.展开更多
Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the q...Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.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
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
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
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
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
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
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
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supported by the National Natural Science Foundation of China(22077101)the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2020WNLOKF023)+4 种基金Natural Science Foundation of Shaanxi Province(2022JM-130)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(2020GXLH-Z-008,2020GXLH-Z-021,2020GXLH-Z-023)the China Postdoctoral Science Foundation(2022M711595,2022M722595)Postdoctoral Research Funding Schemes of Jiangsu Province(2021K036A)The Natural Science Foundation of Ningbo(202003N4049,202003N4065).
文摘Peroxynitrite(ONOO^(-))contributes to oxidative stress and neurodegeneration in Parkinson's disease(PD).Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO^(-)flux and understanding of the ONOO^(-)stress-induced neuropathology of PD.Herein,a novelα-ketoamide-based fluorogenic probe(DFlu)was designed for ONOO^(-)monitoring in multiple PD models.The results demonstrated that DFlu exhibits a fluorescence turn-on response to ONOO^(-)with high specificity and sensitivity.The efficacy of DFlu for intracellular ONOO^(-)imaging was demonstrated systematically.The results showed that DFlu can successfully visualize endogenous and exogenous ONOO^(-)in cells derived from chemical and biochemical routes.More importantly,the two-photon excitation ability of DFlu has been well demonstrated by monitoring exogenous/endogenous ONOO^(-)production and scavenging in live zebraflsh PD models.This work provides a reliable and promisingα-ketoamide-based optical tool for identifying variations of ONOO^(-)in PD models.
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the PICTO project(RFCR-CT-2018-800711)funded by the European Research Fund for Coal and Steel(RFCS)and the Polish Ministry of Science and Higher Education(W93/FBWiS/2018).
文摘The research presented in this paper aimed to analyze the evolution of fractures in strata in relation to the progress of longwall mining.To achieve this objective,an introscopic probe equipped with a highresolution camera was developed,along with additional equipment that enables continuous recording of the internal surfaces of drainage boreholes exceeding 100 m in depth.The probe was utilized to test two methane drainage boreholes in the Z-3b longwall,which operates within the 501/3 coal seam of the Jankowice mine in Poland.Automatic image analysis methods were applied to evaluate the recorded images,based on a newly developed classificationsystem for fractures categorized by size and number.The results were compared with an analysis of changes in the methane capture rate from the drainage boreholes,which correlated with longwall mining progress.A strong correlation was observed between the number of fractures and the lithology of the strata layers.The largest number of fractures and their evolution were recorded in the coal layers,followed by the shale layers,while the sandstone layers exhibited the least number of fractures.Based on parallel measurements of the methane capture rate from the drainage boreholes during the progress of longwall mining,the extent of the strata's fracture zone was determined to range from 6 m to 36 m.Within the fracture zone,the strata are highly fractured,which leads to an increase in methane emissions through seepage and diffusion processes.
基金supported by the National Natural Science Foundation of China (Nos.22177025,21807021,22177026)the Science Fund for Creative Research Groups of the Natural Science Foundation of Hebei Province (No.B2021201038)+1 种基金the Foundation of Hebei University (No.050001-513300201004)the Director’s Foundation of the Key Laboratory of Medicinal Chemistry and Molecular Diagnosis,Ministry of Education,Hebei University (No.MCMDZR2024003)。
文摘Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogenous antioxidants,have been proposed as potential biomarkers for the disease.However,due to the presence of the blood-brain barrier(BBB),fluorescent probes are rarely used to image biothiols in the brain of SCZ models.In this study,a series of fluorescent probes for biothiols were developed using dicyanoisophorone derivatives as fluorophores known for their excellent optical properties,and carboxylic esters as recognition units.A parallel synthesis and rapid screening strategy was employed to construct and optimize these probes.By introducing trifluoromethyl and benzothiazole groups into the fluorophore,the emission wavelength was successfully shifted into the near-infrared region.Additionally,various trifluoromethyl-substituted aromatic and nitrogen heterocyclic compounds were incorporated to optimize the carboxylic esters,thereby improving the probes' reactivity and lipophilicity.Systematic evaluation of the physicochemical characteristics,and optical performance led to the identification of DCIBT-11 as the most promising candidate.DCI-BT-11 demonstrated excellent BBB permeability and a good response to biothiols both in vitro and in vivo.Notably,DCI-BT-11 was used for the first time to visualize biothiol flux and assess the therapeutic effects of the antioxidant N-acetylcysteine(NAC) in the brains of SCZ mouse models,offering new insights into the role of OS in the pathogenesis and treatment of SCZ.
基金supported by the National Key Research and Development Program of China (No.2024YFA1509600)National Natural Science Foundation of China (Nos.22474010 and 22274012)the Fundamental Research Funds for the Central Universities (No.2233300007)。
文摘Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of multiple RSSs significant for evaluating ferroptosis therapy.However,the traditional techniques,including fluorescent(FL) imaging and electrospray ionization-based mass spectrometry(MS) detection,cannot achieve the discrimination of different RSSs.Herein,simultaneous MS detection of multiple RSSs,including cysteine(Cys),homocysteine(Hcy),glutathione(GSH) and hydrogen sulfide(H_(2)S),was obtained upon enhancing ionization efficiency by a fluorescent probe(NBD-O-1).Based on the interaction between NBD-O-1 and RSSs,the complex of RSSs with a fragment of NBD-O-1 can be generated,which can be easily ionized for MS detection in the negative mode.Therefore,the intracellular RSSs can be well detected upon the incubation of He La cells with the probe of NBD-O-1,exhibiting the total RSS levels by the FL imaging and further providing expression of each RSS by enhanced MS detection.Furthermore,the RSSs during ferroptosis in He La cells have been evaluated using the present strategy,demonstrating the potential for ferroptosis examinations.This work has made an unconventional application of a fluorescent probe to enhance the detection of multiple RSSs by MS,providing significant molecular information for addressing the ferroptosis mechanism.
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
文摘Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
基金supported by the National Natural Science Foundation of China(22225805,81400681,32394001,32121005)the Shanghai Science and Technology Innovation Action Plan(22Y11907200,23J21901600)the Innovation Program of Shanghai Municipal Education Commission,Shanghai Municipal Health Commission(2024ZZ2025)。
文摘The thoracic duct(TD),the largest lymphatic vessel in the human body,plays a critical role in returning lymph to the circulatory system.However,its dynamic,distensible nature and concealed anatomical location make intraoperative visualization critically challenging and increase the risk of injury.Real-time,high-resolution assessment of TD leaks remains an urgent clinical need.Here,we present a breakthrough molecular engineering strategy that leverages an intestinally lipophilic fluorescent formulation for dynamic in vivo TD imaging.Our rationally designed cyanine derivative IR790+,known for its rapid membrane permeability and endoplasmic reticulum(ER)targeting localization,demonstrates unprecedented chylomicron affinity,which subsequently transports the dye through the lymphatic system to the TD.Notably,dynamic,high-contrast intraoperative TD imaging is achieved from rat models to swine models.Administered orally as near-infrared(NIR)fluorescent contrast agent,this ultra-stable IR790+@oil formulation,engineered via flash nanoprecipitation,surpasses conventional counterparts by enabling non-invasive,real-time identification of TD.Intriguingly,this first-reported ER-targeting NIR formulation,delivered orally,represents a paradigm shift in fluorescence-guided surgery,significantly improving intraoperative accuracy.
基金the financial support from the National Natural Science Foundation of China(Nos.22377097,22307036,22074114)Natural Science Foundation of Hubei Province of China(Nos.2020CFB623,2021CFB556)Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education(No.LCX202305)。
文摘The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.
基金supported by the Natural Science Foundation of Hubei Province (Nos.2023AFB376 and 2024AFD287)National Key Research and Development Program (No.2023YFC3503804)the National Natural Science Foundation of China (No.22077044)。
文摘Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.
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.
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.
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.
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.
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.
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.
