Fortuitous benefits of activity-based rehabilitation in stem cell-based therapy for spinal cord repair: enhancing graft survival

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.

Activity-Based Costing of Library Services in Universities——A Case Study of a Private University

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.

A Study on Cost Control of Agricultural Water Conservancy Projects Based on Activity-based Costing

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.

Photocaged activity-based probes for improved monitoring of protein S-sulfenylation in living cells

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.

Semi-synthesis of biotin-bearing activity-based ubiquitin probes through sequential enzymatic ligation,N-S acyl transfer and aminolysis reaction

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.

Revealing Formaldehyde Fluxes in Alzheimer's Disease Brain by an Activity-Based Fluorescence Probe

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.

Activity-based smart AIEgens for detection,bioimaging,and therapeutics:Recent progress and outlook

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.

Identification of antimalarial targets of chloroquine by a combined deconvolution strategy of ABPP and MS-CETSA

Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.

ABL教学法及其对思想政治理论课实践教学的启示

高校思想政治理论课实践教学是高校实践育人的重要形式,也是提高高校思想政治教育实效性的重要途径。通识教育课程与思想政治理论课在育人理念上存在本质上的共通,ABL教学法作为哈佛大学新通识教育改革中的重要组成部分,它强调主动学习,重视实践教学,能够有效促进通识教育目标的实现,对我国当前高校思想政治理论课实践教学有一定的借鉴意义。

整合化学和定量蛋白质组学方法用于鉴定药物靶点（英文）

Most drugs exert pharmacological effects through interaction with their target proteins.Therefore,drug target identification is a crucial step towards the understanding of the mechanism of drug action.It is also imperative to study the pharmacodynamics of a known drug,with an aim to discover the potentially unrevealed actions and thus refine its future clinical applications.Currently,drug-target identification is either through in vitro affinity chromatography-based approaches or in vivo activity-based protein profiling(ABPP)approaches.However,these approaches generally face difficulties discriminating specific drug targets from non-specific ones.To address this issue,we have come up with a strategy by coupling iTRAQTM(isobaric tags for relative and absolute quantitation)quantitative proteomics approach with clickable ABPP,to specifically and compre hensively identify drug targets in live cells.Using this approach,we identified the protein targets of andrographolide,a natural product with known anti-inflammation and anti-cancer effects,in live cancer cells.The identified target list not only confirmed the known functions of the drug but also revealed its potential novel application as a tumor metastasis inhibitor.We have also used this strategy,combining with a cleavable probe to identify the protein targets of aspirin and its binding sites.Our results revealed the roles of aspirin ininhibition of protein synthesis and induction of autophagy,which have been functionally validated.Our strategy is widely applicable to the identification of protein targets of covalent drugs.

On Application of ABC Approach in Management of Agri- scientific Research Cost

This paper firstly introduced theoretical background of the Activity-Based Costing(ABC). Then,it analyzed necessity,extension resistance and difficulty of ABC approach in agri-scientific research institutions. Finally,it came up with some recommendations for scientifically learning and steadily promoting ABC method in agri-scientific research field.

Factors Affecting ABB Implementation in PLCC

This paper aims to examine the role and significance of activity-based budgeting(ABB)in developing countries.It provides comparison with the traditional system,and evaluates the possibility of implementing ABB system in private Libyan commercial companies(PLCC).This paper attempts to highlight the factors affecting the implementation of ABB in PLCC.The findings suggest that PLCC still uses traditional system in budget preparation.

Research on Rural Highway Project Construction Management and Maintenance

In this paper,combined with an actual case project,activity-based costing is used to analyze the labor costs,material costs,and the corresponding indirect costs(such as site management fees and taxes)where each cost is analyzed in detailed.Through quantitative comparison,it further determines which business activities are the key cost control objects and proposes targeted implementation plans for actual cost management in the future in order to provide new ideas for improving the implementation efficiency in addition to a reasonable cost control of highway engineering projects.At the same time,through analyzing the situation of highways,different maintenance modes are compared to put forward a more perfect rural road maintenance and management mode.

Celastrol promotes apoptosis of breast cancer MDA-MB-231 cells by targeting HSDL2

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.

A fluorogenic-inhibitor-based probe for profiling and imaging of monoamine oxidase A in live human glioma cells and clinical tissues

Monoamine oxidase A(MAO-A)plays a critical role in the development of glioma and other neurological disorders.Specific analysis of MAO-A activities and its drug interactions in intact tissue is important for biological and pharmacological research,but highly challenging with current chemical tools.Fluorogenic-inhibitor-based probes offer improved selectivity,sensitivity,and effectiveness to image and profile endogenous targets in an activity-based manner from mammalian cells,which are however rare.Herein,we report HD1 as the first fluorogenic-inhibitor-based probe that can selectively label endogenous MAO-A from various mammalian cells and clinical tissues.The probe was delicately designed based on N-propargyl tetrahydropyridine,a small MAO-A-specific fluorogenic and inhibitory war-head,so that the probe becomes fluorescent upon in situ enzymatic oxidation and covalent labeling of MAO-A.With the excellent binding affinity(in vitro K_(i)=285 n M)and fluorogenic properties,HD1 offers a promising approach to simultaneously image endogenous MAO-A activities by super-resolution fluorescence microscopy and study its drug interactions by subsequent activity-based protein profiling,in both live cells and human glioma tissues.

Chemoproteomics identifies Ykt6 as the direct target of schisandrin A for neuroprotection

Schisandrin A is a natural dibenzocyclooctene lignan with potent neuroprotective activity.However,the specific mechanisms or direct target proteins have not been clarified up to now.In this study,we designed and synthesized the probes of schisandrin A with photoreactive diazirine and clickable alkyne to identify its direct target in SH-SY5Y cells by employing activity-based protein profiling(ABPP)technique.Ykt6 was prominent among the 13 proteins obtained with high confidence and we confirmed Ykt6 as the direct target of schisandrin A by CETSA,IF,SPR and knockdown assay.Functionally,schisandrin A protected the cells against the injury induced by glutamate by regulating autophagy via Ykt6.This discovery may provide a novel therapeutic option for various neuronal cell damage-mediated diseases.

Forecasting the spatial and temporal charging demand of fully electrified urban private car transportation based on large-scale traffic simulation

To support power grid operators to detect and evaluate potential power grid congestions due to the electrification of urban private cars,accurate models are needed to determine the charging energy and power demand of battery electric vehicles(BEVs)with high spatial and temporal resolution.Typically,e-mobility traffic simulations are used for this purpose.In particular,activity-based mobility models are used because they individually model the activity and travel patterns of each person in the considered geographical area.In addition to inaccuracies in determining the spatial distribution of BEV charging demand,one main limitation of the activity-based models proposed in the literature is that they rely on data describing traffic flow in the considered area.However,these data are not available for most places in the world.Therefore,this paper proposes a novel approach to develop an activity-based model that overcomes the spatial limitations and does not require traffic flow data as an input parameter.Instead,a route assignment procedure assigns a destination to each BEV trip based on the evaluation of all possible destinations.The basis of this evaluation is the travel distance and speed between the origin of the trip and the destination,as well as the car-access attractiveness and the availability of parking spots at the destinations.The applicability of this model is demonstrated for the urban area of Berlin,Germany,and its 448 sub-districts.For each district in Berlin,both the required daily BEV charging energy demand and the power demand are determined.In addition,the load shifting potential is investigated for an exemplary district.The results show that peak power demand can be reduced by up to 31.7%in comparison to uncontrolled charging.

Click chemistry in the design of AIEgens for biosensing and bioimaging

The development of rapid,selective,and sensitivefluorescent sensors is essential for visualizing and quantifying biological molecules and processes in vitro,ex vitro,and in vivo,which is important for not only fundamental biological studies but the accurate diagnosis of diseases.The emergingfield of activity-based sensing(ABS),a sensing method that utilizes molecular reactivity for analyte detection possesses many advantages including high specificity,sensitivity and accuracy.The aggrega-tion caused quenching phenomenon which occurs in most conventionalfluorophores results in reduced labeling efficiency of the target analytes and low photobleaching resistance,therefore limiting the applications of the ABS strategy.In contrast,aggre-gation induced emission(AIE)active luminogens(AIEgens)provide exceptional molecular frameworks for ABS.Of the many reaction classes utilized in the AIEgen ABS approach,click chemistry has become increasing popular.In this review,the sensing concepts of the ABS approach with AIEgens and the principles of click chemistry are discussed,followed by a systematic summary of the application of specific click chemistry reactions in AIEgen ABS protocols for the detection of an array of target analytes.Furthermore,the utility of click chemistry in the construction of AIEgens for bioimaging will also be showcased throughout the review.

Multi-state supernetworks:recent progress and prospects

Supernetworks have long been adopted to address multi-dimensional choice problems, which are thorny to solve for classic singular networks. Originated from combining transport mode and route choice into a multi-modal network, supernetworks have been extended into multi-state networks to include activity-travel scheduling, centered around activity-based models of travel demand. A key feature of the network extensions is that multiple choice facets pertaining to conducting a full activity program can be modeled in a consistent and integrative fashion. Thus, interdependencies and constraints between related choice facets can be readily captured. Given this advantage of integrity, the modeling of supernetwork has become an emerging topic in transportation research. This paper summarizes the recent progress in modeling multi-state supernetworks and discusses future prospects.