This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demogra...This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demographic and Health Surveys(DHS).Results from both fixed effects(FE)and instrumental variable(IV)estimates show that using non-solid cooking fuel significantly improves the nutrition outcomes of under-five children.Compared with their peers from households mainly using solid fuel,children from households mainly using non-solid fuel exhibit a lower probability of experiencing stunting(by 5.9 percentage points)and being underweight(by 1.2 percentage points).Our further investigation provides evidence for several underlying mechanisms,such as improved indoor air quality,induced reduction in children’s respiratory symptoms,benefits on maternal health,and reduction in maternal time spent on fuel collection or cooking.Heterogenous analyses suggest that the nutrition benefits of using non-solid cooking fuel are more prominent among boys,children above three years old,and those from households of lower socioeconomic status,rural areas,and Southeast Asia.展开更多
Cultural ancient roads,known in Chinese as gudao,serve as heritage trails that carry historical exchanges across various regions in China.Due to their extensive preservation,wide geographical distribution,diverse them...Cultural ancient roads,known in Chinese as gudao,serve as heritage trails that carry historical exchanges across various regions in China.Due to their extensive preservation,wide geographical distribution,diverse thematic variations,and considerable tourist appeal,these paths have emerged as representative heritage trails,increasingly transforming into a novel tourism product experience that is highly favored by tourists and recognized by government authorities.However,research on ancient roads for tourism in China currently lacks a systematic theoretical framework,as well as relevant policies,regulations,and standards to guide their practical development.Therefore,there is a pressing need to draw upon international best practices and conduct foundational research to develop an experience element system that aligns with the perceptions,behaviors,and consumption characteristics of Chinese tourists,thereby advancing theoretical exploration in this field.This study focuses on the representative Ancient Shu Road as a case study and employs a mixed-method approach that integrates qualitative and quantitative research.It aims to construct a tourist-centric scale for the experience elements of ancient road tourism while analyzing the interactive relationship between these experience elements and tourist needs.This study addresses a significant gap in the development of indicator systems for domestic studies of ancient road tourism experiences.Ultimately,the study establishes a comprehensive scale that encompasses three core categories—trail resources and environment,facilities and services,and modes of tourism activities—along with eight primary dimensions:core resources,surrounding cultural environment,surrounding natural environment,tourism reception facilities and services,infrastructure and support services,information facilities and information services,and outdoor and recreational activities.This scale consists of thirty-two specific items,providing a robust reference for future research endeavors.Additionally,the study proposes specific development strategies related to key mechanisms,spatial configuration,and facility construction to enhance the overall development of ancient road tourism.展开更多
While a plethora of studies has been conducted to explore demotivation and its impact on mental health in second language(L2)education,scanty research focuses on demotivation in L2 speaking learning.Particularly,littl...While a plethora of studies has been conducted to explore demotivation and its impact on mental health in second language(L2)education,scanty research focuses on demotivation in L2 speaking learning.Particularly,little research explores the measures to quantify L2 speaking demotivation.The present two-phase study attempts to develop and validate an English Speaking Demotivation Scale(ESDS).To this end,an independent sample of 207 Chinese tertiary learners of English as a Foreign Language(EFL)participated in the development phase,and another group of 188 Chinese EFL learners was recruited for the validation of the scale.Exploratory Factor Analysis(EFA)and Confirmatory Factor Analysis(CFA)were employed to determine the factor structure of the scale.The EFA results revealed a six-factor solution with Teacher-related Factors in Learning Spoken English(TFLSE),Interest and Valence in Learning Spoken English(IVLSE),Self-efficacy in Learning Spoken English(SELSE),Negative Peer Influence in Learning Spoken English(NPILSE),Undesirable Environment for Learning Spoken English(UELSE),and Negative Influence of Assessment and Learning Materials in speaking class(NIALM).In the validation phase,Confirmatory Factor Analysis(CFA)was performed to validate the internal structure of the scale.The CFA results showed that the model fits the data well.Overall,the ESDS is a robust and trustworthy psychometric tool that could be utilized to examine L2 speaking demotivation.Implications for diminishing EFL learners’demotivation,lessening their aversive emotions and promoting their mental health are also discussed.展开更多
Kidney transplantation(KT)is the optimal form of renal replacement therapy for patients with end-stage renal diseases.However,this health service is not available to all patients,especially in developing countries.The...Kidney transplantation(KT)is the optimal form of renal replacement therapy for patients with end-stage renal diseases.However,this health service is not available to all patients,especially in developing countries.The deceased donor KT programs are mostly absent,and the living donor KT centers are scarce.Single-center studies presenting experiences from developing countries usually report a variety of challenges.This review addresses these challenges and the opposing strategies by reviewing the single-center experiences of developing countries.The financial challenges hamper the infrastructural and material availability,coverage of transplant costs,and qualification of medical personnel.The sociocultural challenges influence organ donation,equity of beneficence,and regular follow-up work.Low interests and motives for transplantation may result from high medicolegal responsibilities in KT practice,intense potential psychosocial burdens,complex qualification protocols,and low productivity or compensation for KT practice.Low medical literacy about KT advantages is prevalent among clinicians,patients,and the public.The inefficient organizational and regulatory oversight is translated into inefficient healthcare systems,absent national KT programs and registries,uncoordinated job descriptions and qualification protocols,uncoordinated on-site investigations with regulatory constraints,and the prevalence of commercial KT practices.These challenges resulted in noticeable differences between KT services in developed and developing countries.The coping strategies can be summarized in two main mechanisms:The first mechanism is maximizing the available resources by increasing the rates of living kidney donation,promoting the expertise of medical personnel,reducing material consumption,and supporting the establishment and maintenance of KT programs.The latter warrants the expansion of the public sector and the elimination of non-ethical KT practices.The second mechanism is recruiting external resources,including financial,experience,and training agreements.展开更多
Since 1976, eradicating hunger has become one of the priority objectives of the United Nations, which is included in the Charter of Human Rights;the right to get adequate food. The qualification of food security in ti...Since 1976, eradicating hunger has become one of the priority objectives of the United Nations, which is included in the Charter of Human Rights;the right to get adequate food. The qualification of food security in time and space must analyze not only the three components it covers but also the relationships that these three components maintain. Climate change contributes to food insecurity, but it is not the only factor. To address food insecurity in various forms, greater food security must be combined with improved sustainable agricultural practices with minimal strain on the environment. This review of literature insists on the principles of food security, which in particular allows a better understanding of food insecurity in developing countries and favors a greater contribution of agriculture and food systems in general to nutritional progress.展开更多
Loquat(Eriobotrya japonica Lindl.)is a subtropical evergreen fruit tree that produces fruits with abundant nutrients and medicinal components.Confirming suitable reference genes for a set of loquat samples before qRT-...Loquat(Eriobotrya japonica Lindl.)is a subtropical evergreen fruit tree that produces fruits with abundant nutrients and medicinal components.Confirming suitable reference genes for a set of loquat samples before qRT-PCR experiments is essential for the accurate quantification of gene expression.In this study,eight candidate reference genes were selected from our previously published RNA-seq data,and primers for each candidate reference gene were designed and evaluated.The Cq values of the candidate reference genes were calculated by RT-qPCR in 31 different loquat samples,including 12 subgroups of developing or abiotic-stressed tissues.Different combinations of stable reference genes were screened according to a comprehensive rank,which was synthesized from the results of four algorithms,including the geNorm,NormFinder,BestKeeper andΔCt methods.The screened reference genes were verified by normalizing EjLGA1 in each subgroup.The obtained suitable combinations of reference genes for accurate normalization were GAPDH,EF1αand ACT for floral development;GAPDH,UBCE and ACT for fruit setting;EF1α,GAPDH and eIF2B for fruit ripening;ACT,EF1αand UBCE for leaves under heat stress;eIF2B,UBCE and EF1αfor leaves under freezing stress;EF1α,TUA and UBCE for leaves under salt stress;ACT,EF1αand eIF2B for immature pulp under freezing stress;ACT,UBCE and eIF2B for immature seeds under freezing stress;EF1α,eIF2B and UBCE for both immature pulp and seeds under freezing stress;UBCE,TUB and TUA for red-fleshed fruits under cold-storage stress;eIF2B,RPS3 and TUB for white-fleshed fruits under coldstorage stress;and eIF2B,UBCE and RPS3 for both red-and white-fleshed fruits under cold-storage stress.This study obtained different combinations of stable reference genes for accurate normalization in twelve subgroups of developing or abiotic-stressed tissues in loquat.To our knowledge,this is the first report to obtain stable reference genes for normalizing gene expression of abiotic-stressed tissues in E.japonica.The use of the three most stable reference genes could increase the reliability of future quantification experiments.展开更多
Niyaz studied in China and now works as the assistant manager of the business planning department at CNPC International (Turkmenistan), the biggest gas company overseas of the energy giant China National Petroleum Cor...Niyaz studied in China and now works as the assistant manager of the business planning department at CNPC International (Turkmenistan), the biggest gas company overseas of the energy giant China National Petroleum Corporation (CNPC), in his home country of Turkmenistan. Since he started at the company in 2008, Niyaz has grown from a layman to an expert who has been chosen as the compan's outstanding employee nine times.展开更多
The transcription factor WRINKLED1(WRI1),a member of AP2 gene family that contain typical AP2 domains,has been considered as a master regulator regulating oil biosynthesis in oilseeds.However,the regulatory mechanism ...The transcription factor WRINKLED1(WRI1),a member of AP2 gene family that contain typical AP2 domains,has been considered as a master regulator regulating oil biosynthesis in oilseeds.However,the regulatory mechanism of RcWRI1 in regulating oil accumulation during seed development has not been clearly addressed.Castor bean(Ricinus communis)is one of the most important non-edible oil crops and its seed oils are rich in hydroxy fatty acids,widely applied in industry.In this study,based on castor bean reference genome,three RcWRIs genes(RcWRI1,RcWRI2 and RcWRI3)were identified and the expressed association of RcWRI1 with oil accumulation were determined.Heterologous transformation of RcWRI1 significantly increased oil content in tobacco leaf,confirming that RcWRI1 activate lipid biosynthesis pathway.Using DNA Affinity Purification sequencing(DAP-seq)technology,we confirmed RcWRI1 binding with Transcription Start Site of genes and identified 7961 WRI1-binding candidate genes.Functionally,these identified genes were mainly involved in diverse metabolism pathways(including lipid biosynthesis).Three cis-elements AW-box([CnTnG](n)7[CG])and AW-boxes like([GnAnC](n)6[GC]/[GnAnC](n)7[G])bound with RcWRI1 were identified.Co-expression network analysis of RcWRI1 further found that RcWRI1 might be widely involved in biosynthesis of storage materials during seed development.In particular,yeast one hybrid experiments found that both AP2 domains within RcWRI1 were required in binding targeted genes.These results not only provide new evidence to understand the regulatory mechanism of RcWRI1 in regulation of oil accumulation during castor bean seed development,but also give candidate gene resource for subsequent genetic improvement toward increasing oil content in oilseed crops.展开更多
Objective:To determine the barriers of joining in-vitro fertilization(IVF)programs among infertile couples in developing countries.Methods:This study assessed infertile couples and the barriers or associated factors r...Objective:To determine the barriers of joining in-vitro fertilization(IVF)programs among infertile couples in developing countries.Methods:This study assessed infertile couples and the barriers or associated factors resulting in delayed decision-making of joining IVF program by searching databases PubMed,ScienceDirect,EBSCO,ClinicalKey,and Cochrane Library from inception until December 31,2021.Additional search strategies were snowballing literature search and citation tracking.Results:Eleven articles were included in the scoping review.The cost was the greatest barrier of joining IVF program.Limited access and lack of assisted reproductive technology centers,few qualified infertility trained staff,insufficient government support,low priority in government policy,along with sociocultural factors,such as religion and false beliefs or myths were also majorly considered to be associated obstacles.Conclusions:The main barrier associated with IVF program among infertile couples in developing countries is the high cost of the IVF services.展开更多
This paper aims to explore a simpler and more user-friendly way of generating software based on model-driven development.Previous studies have attempted to generate code from domain models,hoping to reduce coding time...This paper aims to explore a simpler and more user-friendly way of generating software based on model-driven development.Previous studies have attempted to generate code from domain models,hoping to reduce coding time by increasing modeling time.However,as code tools become more advanced,it is challenging to improve efficiency because models are abstract while implementations are concrete.This paper proposes a novel approach that integrates ChatGPT as a plug-in into the whole R&D process and combines it with our code generation tool to enhance R&D efficiency.We have developed some demos to demonstrate the effectiveness of our approach.According to our evaluation,our approach can save more than 90%of the work in implementing the code generation tool,leaving only about 10%of the work for code review,code improvement,and unit testing.展开更多
Environmental impact assessment (EIA), a decision-making process for project appraisal and sustainability adopted globally as an administrative process to identify, predict, evaluate, and monitor projects from their f...Environmental impact assessment (EIA), a decision-making process for project appraisal and sustainability adopted globally as an administrative process to identify, predict, evaluate, and monitor projects from their feasibility, preconstruction, construction, and operation stages to mitigate the adverse impacts and enhance the beneficial impacts for the protection of the affected environment, The study objective is to explore global EIA systems and processes and find shortcomings and implications for making the best instrument or tool to protect the natural environment from man-made activities over the project cycle. For this, the relevant literature on the EIA system and process was reviewed and evaluated through the application of quantitative and qualitative approaches, including the assessment of legal instruments and the adoption of EIA methodologies in developing countries. EIA, initiated in the 1970s in the US and Australia, expanded to developing countries and was amended in East and Southeast Asia from the 1970s to the 2000s. The evaluation assessed that the South Asian countries follow UNEP and IAIA guidelines, utilizing national laws and expert consultations, with screening criteria and administrative processes based on established environmental legislation. Ad hoc, checklist, matrix, network, overlay, cost-benefit analysis, and predictive or simulation in EIA practice are used to assess the environmental impacts of development activities. Failure to recommend major projects undermines public trust and prevents mitigation measures from being implemented. Most developing countries have followed EIA to fulfill the legal requirement with shadow-off monitoring and follow-up rather than to upset, reduce, or compensate for the project impacts as per size, location, and severity of the project area. The research and guidelines outlined in the IAIA principles and process have synthesized the best EIA practices worldwide. Public participation, impact coverage, scientific mitigation, transparent evidence-based approaches, monitoring, follow-up, legitimate approaches, and future appraisal opportunities are major concerns to be included in best EIA practice.展开更多
The digital development rights in developing countries are based on establishing a new international economic order and ensuring equal participation in the digital globalization process to achieve people's well-ro...The digital development rights in developing countries are based on establishing a new international economic order and ensuring equal participation in the digital globalization process to achieve people's well-rounded development in the digital society.The relationship between cross-border data flows and the realization of digital development rights in developing countries is quite complex.Currently,developing countries seek to safeguard their existing digital interests through unilateral regulation to protect data sovereignty and multilateral regulation for cross-border data cooperation.However,developing countries still have to face internal conflicts between national digital development rights and individual and corporate digital development rights during the process of realizing digital development rights.They also encounter external contradictions such as developed countries interfering with developing countries'data sovereignty,developed countries squeezing the policy space of developing countries through dominant rules,and developing countries having conflicts between domestic and international rules.This article argues that balancing openness and security on digital trade platforms is the optimal solution for developing countries to realize their digital development rights.The establishment of WTO digital trade rules should inherently reflect the fundamental demands of developing countries in cross-border data flows.At the same time,given China's dual role as a digital powerhouse and a developing country,it should actively promote the realization of digital development rights in developing countries.展开更多
In this article, the relationship between the knowledge of competitors and the development of new products in the field of capital medical equipment has been investigated. In order to identify the criteria for measuri...In this article, the relationship between the knowledge of competitors and the development of new products in the field of capital medical equipment has been investigated. In order to identify the criteria for measuring competitors’ knowledge and developing new capital medical equipment products, marketing experts were interviewed and then a researcher-made questionnaire was compiled and distributed among the statistical sample of the research. Also, in order to achieve the goals of the research, a questionnaire among 100 members of the statistical community was selected, distributed and collected. To analyze the gathered data, the structural equation modeling (SEM) method was used in the SMART PLS 2 software to estimate the model and then the K-MEAN approach was used to cluster the capital medical equipment market based on the knowledge of actual and potential competitors. The results have shown that the knowledge of potential and actual competitors has a positive and significant effect on the development of new products in the capital medical equipment market. From the point of view of the knowledge of actual competitors, the market of “MRI”, “Ultrasound” and “SPECT” is grouped in the low knowledge cluster;“Pet MRI”, “CT Scan”, “Mammography”, “Radiography, Fluoroscopy and CRM”, “Pet CT”, “SPECT CT” and “Gamma Camera” markets are clustered in the medium knowledge. Finally, “Angiography” and “CBCT” markets are located in the knowledge cluster. From the perspective of knowledge of potential competitors, the market of “angiography”, “mammography”, “SPECT” and “SPECT CT” in the low knowledge cluster, “CT scan”, “radiography, fluoroscopy and CRM”, “pet CT”, “CBCT” markets in the medium knowledge cluster and “MRI”, “pet MRI”, “ultrasound” and “gamma camera” markets in the high knowledge cluster are located.展开更多
Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lili...Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.展开更多
BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lac...BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lack of evidence hampers the acceptance of the technique in clinical practice.CASE SUMMARY A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents.Her parents reported that her hearing level was the same as when she was born.The girl was diagnosed with sensorineural hearing loss(SNHL)by a doctor in the otolaryngology department.After we introduced the foot reflexology project,the parents agreed to participate in the experiment.After 6 months of foot reflexology treatment,the hearing threshold of the girl recovered to a normal level,below 30 dB.CONCLUSION Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.展开更多
The ultrastructure of the epidermis and flesh of apple ( Malus domestica Borkh cv. Red Fuji) fruit was systematically observed during the fruit development via transmission electron microscopy. The results showed t...The ultrastructure of the epidermis and flesh of apple ( Malus domestica Borkh cv. Red Fuji) fruit was systematically observed during the fruit development via transmission electron microscopy. The results showed that, in spite of the ultrastructural changes in many aspects of the developing fruit epidermal cells, it remained almost unchanged throughout the whole developmental process that the cytoplasm was filled with numerous endoplasmic reticula (ER). Most of these endoplasmic reticula were tube_like and rough_ER with enlarged cisterna from which many vesicles were produced. Some of the vesicles were shown to merge into vacuole. Some dynamic Golgi bodies were also found. All the ultrastructural characteristics showed that the epidermal cells have the features of excretory cells. The ultrastructure of the fruit flesh cells at the young fruit stage were shown to be metabolically active, characterized by the presence of numerous clustered plasmodesmata, cisterna enlarged_ and rough_ER filling the cytoplasm, plenty of vesicles and Golgi bodies, indicating their dynamic cellular transport function. Some giant_circular rough_ERs were found. All the ultrastructural features at this early developmental stage should be closely associated with the enlargement of the young fruit. At the rapid growing phase of the fruit the main changes were characterized by: the starch grain_filled amyloplasts, furcating of the single orifice of plasmodesmata, and the cytoplasm enrichment of both the Golgi body_formed vesicles and other vesicles. These features correspond well with those of a photoassimilate sink_cell. An ultrastructural degeneration phenomenon was observed at the fruit ripening stage, but the mitochondria and plasmalemma still remained intact, which might be related to the continuous development of fruit quality during the fruit ripening.展开更多
Salinity stress is a major environmental stress affecting crop productivity,and its negative impact on global food security is only going to increase,due to current climate trends.Salinity tolerance was present in wil...Salinity stress is a major environmental stress affecting crop productivity,and its negative impact on global food security is only going to increase,due to current climate trends.Salinity tolerance was present in wild crop relatives but significantly weakened during domestication.Regaining it back requires a good understanding of molecular mechanisms and traits involved in control of plant ionic and ROS homeostasis.This review summarizes our current knowledge on the role of major plant hormones(auxin,cytokinins,abscisic acid,salicylic acid,and jasmonate)in plants adaptation to soil salinity.We firstly discuss the role of hormones in controlling root tropisms,root growth and architecture(primary root elongation,meristematic activity,lateral root development,and root hairs formation).Hormone-mediated control of uptake and sequestration of key inorganic ions(sodium,potassium,and calcium)is then discussed followed by regulation of cell redox balance and ROS signaling in salt-stressed roots.Finally,the role of epigenetic alterations such as DNA methylation and histone modifications in control of plant ion and ROS homeostasis and signaling is discussed.This data may help develop novel strategies for breeding and cultivating salt-tolerant crops and improving agricultural productivity in saline regions.展开更多
Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been...Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.展开更多
Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have...Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.展开更多
基金This work was supported by the National Natural Science Foundation of China(71861147003 and 71925009).
文摘This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demographic and Health Surveys(DHS).Results from both fixed effects(FE)and instrumental variable(IV)estimates show that using non-solid cooking fuel significantly improves the nutrition outcomes of under-five children.Compared with their peers from households mainly using solid fuel,children from households mainly using non-solid fuel exhibit a lower probability of experiencing stunting(by 5.9 percentage points)and being underweight(by 1.2 percentage points).Our further investigation provides evidence for several underlying mechanisms,such as improved indoor air quality,induced reduction in children’s respiratory symptoms,benefits on maternal health,and reduction in maternal time spent on fuel collection or cooking.Heterogenous analyses suggest that the nutrition benefits of using non-solid cooking fuel are more prominent among boys,children above three years old,and those from households of lower socioeconomic status,rural areas,and Southeast Asia.
文摘Cultural ancient roads,known in Chinese as gudao,serve as heritage trails that carry historical exchanges across various regions in China.Due to their extensive preservation,wide geographical distribution,diverse thematic variations,and considerable tourist appeal,these paths have emerged as representative heritage trails,increasingly transforming into a novel tourism product experience that is highly favored by tourists and recognized by government authorities.However,research on ancient roads for tourism in China currently lacks a systematic theoretical framework,as well as relevant policies,regulations,and standards to guide their practical development.Therefore,there is a pressing need to draw upon international best practices and conduct foundational research to develop an experience element system that aligns with the perceptions,behaviors,and consumption characteristics of Chinese tourists,thereby advancing theoretical exploration in this field.This study focuses on the representative Ancient Shu Road as a case study and employs a mixed-method approach that integrates qualitative and quantitative research.It aims to construct a tourist-centric scale for the experience elements of ancient road tourism while analyzing the interactive relationship between these experience elements and tourist needs.This study addresses a significant gap in the development of indicator systems for domestic studies of ancient road tourism experiences.Ultimately,the study establishes a comprehensive scale that encompasses three core categories—trail resources and environment,facilities and services,and modes of tourism activities—along with eight primary dimensions:core resources,surrounding cultural environment,surrounding natural environment,tourism reception facilities and services,infrastructure and support services,information facilities and information services,and outdoor and recreational activities.This scale consists of thirty-two specific items,providing a robust reference for future research endeavors.Additionally,the study proposes specific development strategies related to key mechanisms,spatial configuration,and facility construction to enhance the overall development of ancient road tourism.
基金the Humanities and Social Sciences Project,China’s Ministry of Education(Grant Number:22YJA740016)the Key Project of Hubei Provincial Department of Education Philosophy and Social Science Research Fund(No.21ZD051)the Teaching and Research Fund of Hubei University of Technology(No.Xiao2022018).
文摘While a plethora of studies has been conducted to explore demotivation and its impact on mental health in second language(L2)education,scanty research focuses on demotivation in L2 speaking learning.Particularly,little research explores the measures to quantify L2 speaking demotivation.The present two-phase study attempts to develop and validate an English Speaking Demotivation Scale(ESDS).To this end,an independent sample of 207 Chinese tertiary learners of English as a Foreign Language(EFL)participated in the development phase,and another group of 188 Chinese EFL learners was recruited for the validation of the scale.Exploratory Factor Analysis(EFA)and Confirmatory Factor Analysis(CFA)were employed to determine the factor structure of the scale.The EFA results revealed a six-factor solution with Teacher-related Factors in Learning Spoken English(TFLSE),Interest and Valence in Learning Spoken English(IVLSE),Self-efficacy in Learning Spoken English(SELSE),Negative Peer Influence in Learning Spoken English(NPILSE),Undesirable Environment for Learning Spoken English(UELSE),and Negative Influence of Assessment and Learning Materials in speaking class(NIALM).In the validation phase,Confirmatory Factor Analysis(CFA)was performed to validate the internal structure of the scale.The CFA results showed that the model fits the data well.Overall,the ESDS is a robust and trustworthy psychometric tool that could be utilized to examine L2 speaking demotivation.Implications for diminishing EFL learners’demotivation,lessening their aversive emotions and promoting their mental health are also discussed.
文摘Kidney transplantation(KT)is the optimal form of renal replacement therapy for patients with end-stage renal diseases.However,this health service is not available to all patients,especially in developing countries.The deceased donor KT programs are mostly absent,and the living donor KT centers are scarce.Single-center studies presenting experiences from developing countries usually report a variety of challenges.This review addresses these challenges and the opposing strategies by reviewing the single-center experiences of developing countries.The financial challenges hamper the infrastructural and material availability,coverage of transplant costs,and qualification of medical personnel.The sociocultural challenges influence organ donation,equity of beneficence,and regular follow-up work.Low interests and motives for transplantation may result from high medicolegal responsibilities in KT practice,intense potential psychosocial burdens,complex qualification protocols,and low productivity or compensation for KT practice.Low medical literacy about KT advantages is prevalent among clinicians,patients,and the public.The inefficient organizational and regulatory oversight is translated into inefficient healthcare systems,absent national KT programs and registries,uncoordinated job descriptions and qualification protocols,uncoordinated on-site investigations with regulatory constraints,and the prevalence of commercial KT practices.These challenges resulted in noticeable differences between KT services in developed and developing countries.The coping strategies can be summarized in two main mechanisms:The first mechanism is maximizing the available resources by increasing the rates of living kidney donation,promoting the expertise of medical personnel,reducing material consumption,and supporting the establishment and maintenance of KT programs.The latter warrants the expansion of the public sector and the elimination of non-ethical KT practices.The second mechanism is recruiting external resources,including financial,experience,and training agreements.
文摘Since 1976, eradicating hunger has become one of the priority objectives of the United Nations, which is included in the Charter of Human Rights;the right to get adequate food. The qualification of food security in time and space must analyze not only the three components it covers but also the relationships that these three components maintain. Climate change contributes to food insecurity, but it is not the only factor. To address food insecurity in various forms, greater food security must be combined with improved sustainable agricultural practices with minimal strain on the environment. This review of literature insists on the principles of food security, which in particular allows a better understanding of food insecurity in developing countries and favors a greater contribution of agriculture and food systems in general to nutritional progress.
基金funded by the Natural Science Foundation of Fujian Province(2021J05240)Fujian Provincial Science and Technology Project(2021N5014,2022N5006)+1 种基金Research Project of Putian Science and Technology Bureau(2021ZP08,2021ZP09,2021ZP10,2021ZP11)Scientific Research Project of Putian University(2018064).
文摘Loquat(Eriobotrya japonica Lindl.)is a subtropical evergreen fruit tree that produces fruits with abundant nutrients and medicinal components.Confirming suitable reference genes for a set of loquat samples before qRT-PCR experiments is essential for the accurate quantification of gene expression.In this study,eight candidate reference genes were selected from our previously published RNA-seq data,and primers for each candidate reference gene were designed and evaluated.The Cq values of the candidate reference genes were calculated by RT-qPCR in 31 different loquat samples,including 12 subgroups of developing or abiotic-stressed tissues.Different combinations of stable reference genes were screened according to a comprehensive rank,which was synthesized from the results of four algorithms,including the geNorm,NormFinder,BestKeeper andΔCt methods.The screened reference genes were verified by normalizing EjLGA1 in each subgroup.The obtained suitable combinations of reference genes for accurate normalization were GAPDH,EF1αand ACT for floral development;GAPDH,UBCE and ACT for fruit setting;EF1α,GAPDH and eIF2B for fruit ripening;ACT,EF1αand UBCE for leaves under heat stress;eIF2B,UBCE and EF1αfor leaves under freezing stress;EF1α,TUA and UBCE for leaves under salt stress;ACT,EF1αand eIF2B for immature pulp under freezing stress;ACT,UBCE and eIF2B for immature seeds under freezing stress;EF1α,eIF2B and UBCE for both immature pulp and seeds under freezing stress;UBCE,TUB and TUA for red-fleshed fruits under cold-storage stress;eIF2B,RPS3 and TUB for white-fleshed fruits under coldstorage stress;and eIF2B,UBCE and RPS3 for both red-and white-fleshed fruits under cold-storage stress.This study obtained different combinations of stable reference genes for accurate normalization in twelve subgroups of developing or abiotic-stressed tissues in loquat.To our knowledge,this is the first report to obtain stable reference genes for normalizing gene expression of abiotic-stressed tissues in E.japonica.The use of the three most stable reference genes could increase the reliability of future quantification experiments.
文摘Niyaz studied in China and now works as the assistant manager of the business planning department at CNPC International (Turkmenistan), the biggest gas company overseas of the energy giant China National Petroleum Corporation (CNPC), in his home country of Turkmenistan. Since he started at the company in 2008, Niyaz has grown from a layman to an expert who has been chosen as the compan's outstanding employee nine times.
基金This work was supported by National Natural Science Foundation of China(grant number 31701465)。
文摘The transcription factor WRINKLED1(WRI1),a member of AP2 gene family that contain typical AP2 domains,has been considered as a master regulator regulating oil biosynthesis in oilseeds.However,the regulatory mechanism of RcWRI1 in regulating oil accumulation during seed development has not been clearly addressed.Castor bean(Ricinus communis)is one of the most important non-edible oil crops and its seed oils are rich in hydroxy fatty acids,widely applied in industry.In this study,based on castor bean reference genome,three RcWRIs genes(RcWRI1,RcWRI2 and RcWRI3)were identified and the expressed association of RcWRI1 with oil accumulation were determined.Heterologous transformation of RcWRI1 significantly increased oil content in tobacco leaf,confirming that RcWRI1 activate lipid biosynthesis pathway.Using DNA Affinity Purification sequencing(DAP-seq)technology,we confirmed RcWRI1 binding with Transcription Start Site of genes and identified 7961 WRI1-binding candidate genes.Functionally,these identified genes were mainly involved in diverse metabolism pathways(including lipid biosynthesis).Three cis-elements AW-box([CnTnG](n)7[CG])and AW-boxes like([GnAnC](n)6[GC]/[GnAnC](n)7[G])bound with RcWRI1 were identified.Co-expression network analysis of RcWRI1 further found that RcWRI1 might be widely involved in biosynthesis of storage materials during seed development.In particular,yeast one hybrid experiments found that both AP2 domains within RcWRI1 were required in binding targeted genes.These results not only provide new evidence to understand the regulatory mechanism of RcWRI1 in regulation of oil accumulation during castor bean seed development,but also give candidate gene resource for subsequent genetic improvement toward increasing oil content in oilseed crops.
文摘Objective:To determine the barriers of joining in-vitro fertilization(IVF)programs among infertile couples in developing countries.Methods:This study assessed infertile couples and the barriers or associated factors resulting in delayed decision-making of joining IVF program by searching databases PubMed,ScienceDirect,EBSCO,ClinicalKey,and Cochrane Library from inception until December 31,2021.Additional search strategies were snowballing literature search and citation tracking.Results:Eleven articles were included in the scoping review.The cost was the greatest barrier of joining IVF program.Limited access and lack of assisted reproductive technology centers,few qualified infertility trained staff,insufficient government support,low priority in government policy,along with sociocultural factors,such as religion and false beliefs or myths were also majorly considered to be associated obstacles.Conclusions:The main barrier associated with IVF program among infertile couples in developing countries is the high cost of the IVF services.
基金fully supported by the Natural Science Foundation of Hubei Province in China(Grant No.2021CFB482)Basic Research Science and Technology Project of Xiangyang(High-tech Domain 2022ABH007013)Hubei Superior and Distinctive Discipline Group of“New Energy Vehicle and Smart Transportation”。
文摘This paper aims to explore a simpler and more user-friendly way of generating software based on model-driven development.Previous studies have attempted to generate code from domain models,hoping to reduce coding time by increasing modeling time.However,as code tools become more advanced,it is challenging to improve efficiency because models are abstract while implementations are concrete.This paper proposes a novel approach that integrates ChatGPT as a plug-in into the whole R&D process and combines it with our code generation tool to enhance R&D efficiency.We have developed some demos to demonstrate the effectiveness of our approach.According to our evaluation,our approach can save more than 90%of the work in implementing the code generation tool,leaving only about 10%of the work for code review,code improvement,and unit testing.
文摘Environmental impact assessment (EIA), a decision-making process for project appraisal and sustainability adopted globally as an administrative process to identify, predict, evaluate, and monitor projects from their feasibility, preconstruction, construction, and operation stages to mitigate the adverse impacts and enhance the beneficial impacts for the protection of the affected environment, The study objective is to explore global EIA systems and processes and find shortcomings and implications for making the best instrument or tool to protect the natural environment from man-made activities over the project cycle. For this, the relevant literature on the EIA system and process was reviewed and evaluated through the application of quantitative and qualitative approaches, including the assessment of legal instruments and the adoption of EIA methodologies in developing countries. EIA, initiated in the 1970s in the US and Australia, expanded to developing countries and was amended in East and Southeast Asia from the 1970s to the 2000s. The evaluation assessed that the South Asian countries follow UNEP and IAIA guidelines, utilizing national laws and expert consultations, with screening criteria and administrative processes based on established environmental legislation. Ad hoc, checklist, matrix, network, overlay, cost-benefit analysis, and predictive or simulation in EIA practice are used to assess the environmental impacts of development activities. Failure to recommend major projects undermines public trust and prevents mitigation measures from being implemented. Most developing countries have followed EIA to fulfill the legal requirement with shadow-off monitoring and follow-up rather than to upset, reduce, or compensate for the project impacts as per size, location, and severity of the project area. The research and guidelines outlined in the IAIA principles and process have synthesized the best EIA practices worldwide. Public participation, impact coverage, scientific mitigation, transparent evidence-based approaches, monitoring, follow-up, legitimate approaches, and future appraisal opportunities are major concerns to be included in best EIA practice.
基金a preliminary result of the Chinese Government Scholarship High-level Graduate Program sponsored by China Scholarship Council(Program No.CSC202206310052)。
文摘The digital development rights in developing countries are based on establishing a new international economic order and ensuring equal participation in the digital globalization process to achieve people's well-rounded development in the digital society.The relationship between cross-border data flows and the realization of digital development rights in developing countries is quite complex.Currently,developing countries seek to safeguard their existing digital interests through unilateral regulation to protect data sovereignty and multilateral regulation for cross-border data cooperation.However,developing countries still have to face internal conflicts between national digital development rights and individual and corporate digital development rights during the process of realizing digital development rights.They also encounter external contradictions such as developed countries interfering with developing countries'data sovereignty,developed countries squeezing the policy space of developing countries through dominant rules,and developing countries having conflicts between domestic and international rules.This article argues that balancing openness and security on digital trade platforms is the optimal solution for developing countries to realize their digital development rights.The establishment of WTO digital trade rules should inherently reflect the fundamental demands of developing countries in cross-border data flows.At the same time,given China's dual role as a digital powerhouse and a developing country,it should actively promote the realization of digital development rights in developing countries.
文摘In this article, the relationship between the knowledge of competitors and the development of new products in the field of capital medical equipment has been investigated. In order to identify the criteria for measuring competitors’ knowledge and developing new capital medical equipment products, marketing experts were interviewed and then a researcher-made questionnaire was compiled and distributed among the statistical sample of the research. Also, in order to achieve the goals of the research, a questionnaire among 100 members of the statistical community was selected, distributed and collected. To analyze the gathered data, the structural equation modeling (SEM) method was used in the SMART PLS 2 software to estimate the model and then the K-MEAN approach was used to cluster the capital medical equipment market based on the knowledge of actual and potential competitors. The results have shown that the knowledge of potential and actual competitors has a positive and significant effect on the development of new products in the capital medical equipment market. From the point of view of the knowledge of actual competitors, the market of “MRI”, “Ultrasound” and “SPECT” is grouped in the low knowledge cluster;“Pet MRI”, “CT Scan”, “Mammography”, “Radiography, Fluoroscopy and CRM”, “Pet CT”, “SPECT CT” and “Gamma Camera” markets are clustered in the medium knowledge. Finally, “Angiography” and “CBCT” markets are located in the knowledge cluster. From the perspective of knowledge of potential competitors, the market of “angiography”, “mammography”, “SPECT” and “SPECT CT” in the low knowledge cluster, “CT scan”, “radiography, fluoroscopy and CRM”, “pet CT”, “CBCT” markets in the medium knowledge cluster and “MRI”, “pet MRI”, “ultrasound” and “gamma camera” markets in the high knowledge cluster are located.
基金supported by the National Key Research and Development Program of China(2022YFD1200500)the Fundamental Research Funds for the Central Universities(KYZZ2022004)+1 种基金the Project for Crop Germplasm Resources Conservation of Jiangsu(2021-SJ-011)the High Level Talent Project of the Top Six Talents in Jiangsu(NY-077)。
文摘Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.
基金Graduate Student Project of Xi’an International Studies University,No.2021BS012Nanchong City-Universities Project,No.22SXCXTD0004.
文摘BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lack of evidence hampers the acceptance of the technique in clinical practice.CASE SUMMARY A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents.Her parents reported that her hearing level was the same as when she was born.The girl was diagnosed with sensorineural hearing loss(SNHL)by a doctor in the otolaryngology department.After we introduced the foot reflexology project,the parents agreed to participate in the experiment.After 6 months of foot reflexology treatment,the hearing threshold of the girl recovered to a normal level,below 30 dB.CONCLUSION Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.
文摘The ultrastructure of the epidermis and flesh of apple ( Malus domestica Borkh cv. Red Fuji) fruit was systematically observed during the fruit development via transmission electron microscopy. The results showed that, in spite of the ultrastructural changes in many aspects of the developing fruit epidermal cells, it remained almost unchanged throughout the whole developmental process that the cytoplasm was filled with numerous endoplasmic reticula (ER). Most of these endoplasmic reticula were tube_like and rough_ER with enlarged cisterna from which many vesicles were produced. Some of the vesicles were shown to merge into vacuole. Some dynamic Golgi bodies were also found. All the ultrastructural characteristics showed that the epidermal cells have the features of excretory cells. The ultrastructure of the fruit flesh cells at the young fruit stage were shown to be metabolically active, characterized by the presence of numerous clustered plasmodesmata, cisterna enlarged_ and rough_ER filling the cytoplasm, plenty of vesicles and Golgi bodies, indicating their dynamic cellular transport function. Some giant_circular rough_ERs were found. All the ultrastructural features at this early developmental stage should be closely associated with the enlargement of the young fruit. At the rapid growing phase of the fruit the main changes were characterized by: the starch grain_filled amyloplasts, furcating of the single orifice of plasmodesmata, and the cytoplasm enrichment of both the Golgi body_formed vesicles and other vesicles. These features correspond well with those of a photoassimilate sink_cell. An ultrastructural degeneration phenomenon was observed at the fruit ripening stage, but the mitochondria and plasmalemma still remained intact, which might be related to the continuous development of fruit quality during the fruit ripening.
基金supported by Australian Research Council and National Natural Science Foundation of China grants to Sergey Shabala。
文摘Salinity stress is a major environmental stress affecting crop productivity,and its negative impact on global food security is only going to increase,due to current climate trends.Salinity tolerance was present in wild crop relatives but significantly weakened during domestication.Regaining it back requires a good understanding of molecular mechanisms and traits involved in control of plant ionic and ROS homeostasis.This review summarizes our current knowledge on the role of major plant hormones(auxin,cytokinins,abscisic acid,salicylic acid,and jasmonate)in plants adaptation to soil salinity.We firstly discuss the role of hormones in controlling root tropisms,root growth and architecture(primary root elongation,meristematic activity,lateral root development,and root hairs formation).Hormone-mediated control of uptake and sequestration of key inorganic ions(sodium,potassium,and calcium)is then discussed followed by regulation of cell redox balance and ROS signaling in salt-stressed roots.Finally,the role of epigenetic alterations such as DNA methylation and histone modifications in control of plant ion and ROS homeostasis and signaling is discussed.This data may help develop novel strategies for breeding and cultivating salt-tolerant crops and improving agricultural productivity in saline regions.
基金supported by funding from the Bluesand Foundation,Alzheimer's Association(AARG-21-852072 and Bias Frangione Early Career Achievement Award)to EDan Australian Government Research Training Program scholarship and the University of Sydney's Brain and Mind Centre fellowship to AH。
文摘Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.
基金supported by the sup-project of National Key R&D Program of China,No.2018YFA0108602CAMS Innovation Fund for Medical Sciences,No.CIFMS,2021-I2M-C&T-B-016National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-112(all to JG).
文摘Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.